Alterations of aorta intima and media transcriptome in swine fed high-fat diet over 1-year follow-up period and of the switch to normal diet.

BACKGROUND AND AIM: We previously showed that 12-month high-fat diet (HFD) in pigs led to fattening and increased artery intima-media-thickness, which were partly reversed after 3-month return to control diet (CD). The aim of this study was to decipher underlying mechanism of action by using transcriptomic analyses of intima and media of aorta. METHODS AND RESULTS: Thirty-two pigs were divided into three groups: CD for 12 months; HFD for 12 months; switch diet group (regression diet; RD): HFD for 9 months followed by CD for 3 months. After 12 months, RNA was isolated from aorta intima and media for nutrigenomic analyses. HFD significantly affected gene expression in intima, while RD gene expression profile was distinct from the CD group. This suggests that switch to CD is not sufficient to correct gene expression alterations induced by HFD but counteracted expression of a group of genes. HFD also affected gene expression in media and as for intima, the expression profile of media of pigs on RD differed from that of these on CD. CONCLUSIONS: This study revealed nutrigenomic modifications induced by long-term HFD consumption on arterial intima and media. The return to CD was not sufficient to counteract the genomic effect of HFD.

Ice front blocking of ocean heat transport to an Antarctic ice shelf.

Mass loss from the Antarctic Ice Sheet to the ocean has increased in recent decades, largely because the thinning of its floating ice shelves has allowed the outflow of grounded ice to accelerate1,2. Enhanced basal melting of the ice shelves is thought to be the ultimate driver of change2,3, motivating a recent focus on the processes that control ocean heat transport onto and across the seabed of the Antarctic continental shelf towards the ice4-6. However, the shoreward heat flux typically far exceeds that required to match observed melt rates2,7,8, suggesting that other critical controls exist. Here we show that the depth-independent (barotropic) component of the heat flow towards an ice shelf is blocked by the marked step shape of the ice front, and that only the depth-varying (baroclinic) component, which is typically much smaller, can enter the sub-ice cavity. Our results arise from direct observations of the Getz Ice Shelf system and laboratory experiments on a rotating platform. A similar blocking of the barotropic component may occur in other areas with comparable ice-bathymetry configurations, which may explain why changes in the density structure of the water column have been found to be a better indicator of basal melt rate variability than the heat transported onto the continental shelf9. Representing the step topography of the ice front accurately in models is thus important for simulating ocean heat fluxes and induced melt rates.

Optical and magnetic properties of the ground state of Cr3+ doping ions in REM3(BO3)4 single crystals.

New data about the state of Cr3+ doping ions in a single crystal of YGa3(BO3)4 have been obtained by studying different methods. Using electron paramagnetic resonance, it was found that the Cr3+ ions substitute the trivalent gallium ions. The obtained spin Hamiltonian parameters of the Cr3+ ions in the YGa3(BO3)4 single crystal (g = 1.9743 ± 0.0004; D = -0.465 ± 0.001 cm-1; E = -0.013 ± 0.001 cm-1) were analyzed and compared with those in TmAl3(BO3)4, EuAl3(BO3)4, and YAl3(BO3)4. The deviation of the Z-axis in the spectrum from the crystallographic axis С3 is 1,7 degrees in YGa3(BO3)4. In situ X-ray diffraction was used to study the structural and elastic properties of huntite-type borates in the temperature range of RT-1073 K. In the radioluminescence (RL) spectra, the Cr3+-related emission bands were observed in the red wavelength range, and the presence of other defect-related bands was also registered in some cases. Thermally stimulated luminescence (TSL) glow curves were acquired over a wide temperature range, and the trap depths of the most prominent bands were calculated. The 11B NMR spectra show that two nonequivalent spectral components exist for BO3 structural elements.

Hepatic adenoma during pregnancy and anesthetic management.

We report the case of a 24-year-old woman with a large hepatic adenoma diagnosed in the third trimester of pregnancy. The adenoma was at risk of rupture. She underwent scheduled preterm cesarean delivery under combined spinal-epidural anesthesia, followed by transarterial embolization on post-partum day six. Definitive resection of the adenoma took place two months postpartum.

Erratum: Prediction for a Four-Neutron Resonance [Phys. Rev. Lett. 117, 182502 (2016)].

This corrects the article DOI: 10.1103/PhysRevLett.117.182502.

Gene Expression in the Three-Spined Stickleback (Gasterosteus aculeatus) of Marine and Freshwater Ecotypes.

Three-spine stickleback (Gasterosteus aculeatus) is a well-known model organism that is routinely used to explore microevolution processes and speciation, and the number of studies related to this fish has been growing recently. The main reason for the increased interest is the processes of freshwater adaptation taking place in natural populations of this species. Freshwater three-spined stickleback populations form when marine water three-spined sticklebacks fish start spending their entire lifecycle in freshwater lakes and streams. To boot, these freshwater populations acquire novel biological traits during their adaptation to a freshwater environment. The processes taking place in these populations are of great interest to evolutionary biologists. Here, we present differential gene expression profiling in G. aculeatus gills, which was performed in marine and freshwater populations of sticklebacks. In total, 2,982 differentially expressed genes between marine and freshwater populations were discovered. We assumed that differentially expressed genes were distributed not randomly along stickleback chromosomes and that they are regularly observed in the "divergence islands" that are responsible for stickleback freshwater adaptation.

The α2 isoform Na,K-ATPase modulates contraction of rat mesenteric small artery via cSrc-dependent Ca2+ sensitization.

AIMS: The Na,K-ATPase is involved in a large number of regulatory activities including cSrc-dependent signalling. Upon inhibition of the Na,K-ATPase with ouabain, cSrc activation is shown to occur in many cell types. This study tests the hypothesis that acute potentiation of agonist-induced contraction by ouabain is mediated through Na,K-ATPase-cSrc signalling-dependent sensitization of vascular smooth muscle cells to Ca2+ . METHODS: Agonist-induced rat mesenteric small artery contraction was examined in vitro under isometric conditions and in vivo in anaesthetized rats. Arterial wall tension and [Ca2+ ]i in vascular smooth muscle cells were measured simultaneously. Changes in cSrc and myosin phosphatase targeting protein 1 (MYPT1) phosphorylation were analysed by Western blot. Protein expression was examined with immunohistochemistry. The α1 and α2 isoforms of the Na,K-ATPase were transiently downregulated by siRNA transfection in vivo. RESULTS: Ten micromolar ouabain, but not digoxin, potentiated contraction to noradrenaline. This effect was not endothelium-dependent. Ouabain sensitized smooth muscle cells to Ca2+ , and this was associated with increased phosphorylation of cSrc and MYPT1. Inhibition of tyrosine kinase by genistein, PP2 or pNaKtide abolished the potentiating effect of ouabain on arterial contraction and Ca2+ sensitization. Downregulation of the Na,K-ATPase α2 isoform made arterial contraction insensitive to ouabain and tyrosine kinase inhibition. CONCLUSION: Data suggest that micromolar ouabain potentiates agonist-induced contraction of rat mesenteric small artery via Na,K-ATPase-dependent cSrc activation, which increases Ca2+ sensitization of vascular smooth muscle cells by MYPT1 phosphorylation. This mechanism may be critical for acute control of vascular tone.

Prevalence of hypertension and prehypertension in children and adolescents with intellectual disability in southeastern Poland.

BACKGROUND: There is insufficient information on the prevalence of hypertension (HPT) among children and adolescents with ID. AIM: The aim of this study was to determine the prevalence of HPT in children and adolescents with ID in comparison with the control group, which accounted for children and adolescents without ID. METHODS: The study included 568 students with ID, aged from 7 to 18, attending special education institutions in southeastern Poland. The control group consisted of 568 students (matched to the study group for age and gender) without ID, attending randomly selected elementary and secondary schools located in the same area. Blood pressure was measured in compliance with the European Society of Hypertension recommendations. RESULTS: The overall prevalence of HPT and pre-HPT in children and adolescents with ID were 18.5 and 20.6% respectively. Prevalence of HPT and pre-HPT in children and adolescents without ID were 5.8 and 18.5% respectively. Children and adolescents with a higher level of ID were found to be at a greater risk of HPT. An excessive body mass and older age were predisposing factors to a significantly higher prevalence of HPT in children and adolescents with ID. CONCLUSION: The prevalence of HPT among students with ID was more than three times higher than in the general population. The level of ID, age, sex and body mass significantly correlated with HPT in the study group.

Metagenomic analysis of microbial community of a parasitoid wasp Megaphragma amalphitanum.

The vast majority of multicellular organisms coexist with bacterial symbionts that may play various roles during their life cycle. Parasitoid wasp Megaphragma amalphitanum (Hymenoptera: Trichogrammatidae) belongs to the smallest known insects whose size is comparable with some bacteria. Using 16S rRNA gene sequencing and Whole Genome Sequencing (WGS), we described microbiota diversity for this arthropod and its potential impact on their lifecycle. Metagenomic sequences were deposited to SRA database which is available at NCBI with accession number SRX2363723 and SRX2363724. We found that small body size and limited lifespan do not lead to a significant reduction of bacterial symbionts diversity. At the same time, we show here a specific feature of microbiota composition in M. amalphitanum - the absence of the Rickettsiaceae family representatives that are known to cause sex-ratio distortion in arthropods and well represented in other populations of parasitoid wasps.

Prediction for a Four-Neutron Resonance.

We utilize various ab initio approaches to search for a low-lying resonance in the four-neutron (4n) system using the JISP16 realistic NN interaction. Our most accurate prediction is obtained using a J-matrix extension of the no-core shell model and suggests a 4n resonant state at an energy near E_{r}=0.8 MeV with a width of approximately Γ=1.4 MeV.

Use of electronic health records by child primary healthcare providers in Europe.

BACKGROUND: There is limited data on the use and functionality level of electronic health records (EHRs) supporting primary child health care in Europe. Our objective was to determine European primary child healthcare providers' use of EHRs, and functionality level of the systems used. METHODS: European primary care paediatricians, paediatric subspecialists and family doctors were invited by European Academy of Paediatrics Research in Ambulatory Setting Network (EAPRASnet) country coordinators to complete a web-based survey on the use of EHRs and the systems' functionalities. Binomial logistic analysis has been used to evaluate the effect of specialty and type of practice on the use of EHRs. RESULTS: The survey was completed by 679 child primary healthcare providers (response rate 53%). Five hundred and fifty four responses coming from 10 predominant countries were taken for further analysis. EHR use by respondents varied widely between countries, all electronic type use ranging between 7% and 97%. There was no significant difference in EHR use between group practice and solo practitioners, or between family doctors and primary care paediatricians. History and physical examination can be properly recorded by respondents in most countries. However, growth chart plotting capacity in some countries ranges between 22% and 50%. Vaccination recording capacity varies between 50% and 100%, and data exchange capacity with immunization databases is mostly limited, ranging between 0% and 54%. CONCLUSIONS: There is marked heterogeneity in the use and functionalities of EHRs used among child primary child healthcare providers in Europe. More importantly, lack of critical paediatric supportive functionalities like growth tracking and vaccination status has been documented in some countries. There is a need to explore the reasons for these findings, and to develop a cross European paediatric EHR standards.

Varying effects of EGF, HGF and TGFß on formation of invadopodia and invasiveness of melanoma cell lines of different origin.

The understanding of melanoma malignancy mechanisms is essential for patient survival, because melanoma is responsible for ca. 75% of deaths related to skin cancers. Enhanced formation of invadopodia and extracellular matrix (ECM) degradation are two important drivers of cell invasion, and actin dynamics facilitate protrusive activity by providing a driving force to push through the ECM. We focused on the influence of epidermal growth factor (EGF), hepatocyte growth factor (HGF) and transforming growth factor ß (TGFß) on melanoma cell invasiveness, since they are observed in the melanoma microenvironment. All three factors stimulated invasion of A375 and WM1341D cells derived from primary tumor sites. In contrast, only EGF and HGF stimulated invasion of WM9 and Hs294T cells isolated from lymph node metastases. Enhanced formation of invadopodia and ECM degradation underlie the increased amount of invasive cells after stimulation with the tested agents. Generally, a rise in invasive potential was accompanied by a decrease in actin polymerization state (F:G ratio). The F:G ratio remained unchanged or was even increased in metastatic cell lines treated with TGFß. Our findings indicate that the effects of stimulation with EGF, HGF and TGFß on melanoma cell invasiveness could depend on melanoma cell progression stage.

Genomic Study of Cardiovascular Continuum Comorbidity.

Comorbidity or a combination of several diseases in the same individual is a common and widely investigated phenomenon. However, the genetic background for non-random disease combinations is not fully understood. Modern technologies and approaches to genomic data analysis enable the investigation of the genetic profile of patients burdened with several diseases (polypathia, disease conglomerates) and its comparison with the profiles of patients with single diseases. An association study featuring three groups of patients with various combinations of cardiovascular disorders and a control group of relatively healthy individuals was conducted. Patients were selected as follows: presence of only one disease, ischemic heart disease (IHD); a combination of two diseases, IHD and arterial hypertension (AH); and a combination of several diseases, including IHD, AH, type 2 diabetes mellitus (T2DM), and hypercholesterolemia (HC). Genotyping was performed using the "My Gene" genomic service (www.i-gene.ru). An analysis of 1,400 polymorphic genetic variants and their associations with the studied phenotypes are presented. A total of 14 polymorphic variants were associated with the phenotype "IHD only," including those in the APOB, CD226, NKX2-5, TLR2, DPP6, KLRB1, VDR, SCARB1, NEDD4L, and SREBF2 genes, and intragenic variants rs12487066, rs7807268, rs10896449, and rs944289. A total of 13 genetic markers were associated with the "IHD and AH" phenotype, including variants in the BTNL2, EGFR, CNTNAP2, SCARB1, and HNF1A genes, and intragenic polymorphisms rs801114, rs10499194, rs13207033, rs2398162, rs6501455, and rs1160312. A total of 14 genetic variants were associated with a combination of several diseases of cardiovascular continuum (CVC), including those in the TAS2R38, SEZ6L, APOA2, KLF7, CETP, ITGA4, RAD54B, LDLR, and MTAP genes, along with intragenic variants rs1333048, rs1333049, and rs6501455. One common genetic marker was identified for the "IHD only" and "IHD and AH" phenotypes: rs4765623 in the SCARB1 gene; two common genetic markers, rs663048 in SEZ6L and intragenic rs6501455, were identified for the "IHD and AH" phenotype and a combination of several diseases (syntropy); there were no common genetic markers for the "syntropy" and "IHD only" phenotypes. Classificatory analysis of the relationships between the associated genes and metabolic pathways revealed that lipid-metabolizing genes are involved in the development of all three CVC variants, whereas immunity-response genes are specific to the "IHD only" phenotype. The study demonstrated that comorbidity presents additional challenges in association studies of disease predisposition, since the genetic profile of combined forms of pathology can be markedly different from those for isolated "single" forms of a disease.

Individual genome sequencing identified a novel enhancer element in exon 7 of the CSFR1 gene by shift of expressed allele ratios.

The sequencing of individual genetic information may provide a powerful tool for elucidating the mechanism by which individual SNPs affect promoter function. Here, we assessed the genome of a Russian male that was previously sequenced. The RNA-Seq data from blood cells revealed 234 candidate transcripts with shifts of greater than 1.5-fold from equal biallelic transcription. Of these genes, the CSF1R gene had variations in genic regions that affected the association of RORalpha with its target binding site in vivo. The results of a reporter assay confirmed that a single nucleotide substitution, rs2228422, within the RORalpha recognition motif altered the ability of the enhancer to regulate CSF1R gene transcription. Notably, 31% of Europeans and only 3% of Asians are homozygous for a RORalpha responsive "A" allele, but no association with diseases of rs2228422 has been found thus far.

Proteome of spleen CD4 lymphocytes in mouse preimplantation pregnancy.

Pregnancy exerts profound impact on female immune system. The first signs of pregnancy recognition by immune system are observed even before implantation. The most visible effects are present in the local compartment, i.e. in uterine draining lymph nodes and the decidua, while peripheral changes are less obvious. In our recent paper we indicated that costimulation phenotype of APCs in spleens of female mice during the preimplantation period of pregnancy differs from mice in pseudopregnancy. However, the effect of differential costimulation in the context of the T lymphocyte function at periphery in early pregnancy is still unknown. For that reason, we decided to investigate global protein expression in splenic CD4(+) lymphocytes in order to identify and validate the most important biomarkers characteristic for the preimplantation period of pregnancy at periphery. Two-dimensional electrophoresis (2-DE) and mass spectrometry (MS) were utilized to analyze the protein expression pattern of magnetically sorted CD4(+) lymphocytes from spleens of pregnant and pseudopregnant females at 3.5 days after mating. The first goal of this study was to create a 2-DE map of the splenic CD4(+) T cells of pregnant mice. As a result, 106 protein spots from 373 were identified using MS. The comparison of lymphocyte protein patterns between pregnant and pseudopregnant mice depicted differential expression of 11 identified proteins belonging to the group of proteins involved in cytoskeletal structure, cell motility and metabolism. Profoundly diminished expression of cofilin-1, F-actin capping protein subunit alpha and malate dehydrogenase proteins in lymphocytes of pregnant mice indicates that preimplantation pregnancy could change the activation state of peripheral CD4(+) lymphocytes.

A comparison of outcomes after K-wire fixation of distal radius fractures with and without associated ulnar styloid fracture.

PURPOSE: A prospective study was carried out to compare outcomes after K-wire fixation of distal radius fractures without and with associated ulnar styloid fracture, but without fixation of the styloid fracture. PATIENTS AND METHODS: 70 patients, 60 women (86%) and 10 men (14%) with a mean age of 63 years were enrolled. 35 patients had an isolated fracture of the distal radius and 35 had an associated fracture of the ulnar styloid. All patients underwent percutaneous, "augmented" K-wire fixation of the distal radius fracture; the ulnar styloid fracture was left untreated. The patients were followed-up at 3 and 6 months. The stability of the distal radioulnar joint and the DASH scores were considered to be primary outcome measures. RESULTS: Instability of the distal radioulnar joint was diagnosed in 2 patients with ulnar styloid fracture. No significant and clinically meaningful differences were found between the groups in clinical (pain, wrist mobility, grip strength, DASH score) and radiological outcomes. The rate of non-union of the ulnar styloid was 77% at final assessment. CONCLUSION: An unrepaired ulnar styloid fracture does not affect the outcome of a distal radius fracture which is fixed by the "augmented" K-wire method.