Search

Intrauterine growth restriction (IUGR) occurs both in humans and domestic species. It has a particularly high incidence in pigs, and is a leading cause of neonatal morbidity and mortality as well as impaired postnatal growth. A key feature of IUGR is impaired muscle development, resulting in decreased meat quality. Understanding the developmental origins of IUGR, particularly at the molecular level, is important for developing effective strategies to mitigate its economic impact on the pig industry and animal welfare. The aim of this study was to characterise transcriptional profiles in the muscle of growth restricted pig foetuses at different gestational days (GD; gestational length ~ 115 days), focusing on selected genes (related to development, tissue injury and metabolism) that were previously identified as dysregulated in muscle of GD90 fetuses. Muscle samples were collected from the lightest foetus (L) and the sex-matched foetus with weight closest to the litter average (AW) from each of 22 Landrace x Large White litters corresponding to GD45 (n = 6), GD60 (n = 8) or GD90 (n = 8), followed by analyses, using RT-PCR and protein immunohistochemistry, of selected gene targets. Expression of the developmental genes, MYOD, RET and ACTN3 were markedly lower, whereas MSTN expression was higher, in the muscle of L relative to AW littermates beginning on GD45. Levels of all tissue injury-associated transcripts analysed (F5, PLG, KNG1, SELL, CCL16) were increased in L muscle on GD60 and, most prominently, on GD90. Among genes involved in metabolic regulation, KLB was expressed at higher levels in L than AW littermates beginning on GD60, whereas both IGFBP1 and AHSG were higher in L littermates on GD90 but only in males. Furthermore, the expression of genes specifically involved in lipid, hexose sugar or iron metabolism increased or, in the case of UCP3, decreased in L littermates on GD60 (UCP3, APOB, ALDOB) or GD90 (PNPLA3, TF), albeit in the case of ALDOB this only involved females. In conclusion, marked dysregulation of genes with critical roles in development in L foetuses can be observed from GD45, whereas for a majority of transcripts associated with tissue injury and metabolism differences between L and AW foetuses were apparent by GD60 or only at GD90, thus identifying different developmental windows for different types of adaptive responses to IUGR in the muscle of porcine foetuses. [ABSTRACT FROM AUTHOR]

11β-Hydroxysteroid dehydrogenase 1 (11βHSD1) is a drug target to attenuate adverse effects of chronic glucocorticoid excess. It catalyses intracellular regeneration of active glucocorticoids in tissues including brain, liver and adipose tissue (coupled to hexose-6-phosphate dehydrogenase, H6PDH). 11βHSD1 activity in individual tissues is thought to contribute significantly to glucocorticoid levels at those sites, but its local contribution vs glucocorticoid delivery via the circulation is unknown. Here, we hypothesised that hepatic 11βHSD1 would contribute significantly to the circulating pool. This was studied in mice with Cre-mediated disruption of Hsd11b1 in liver (Alac-Cre) vs adipose tissue (aP2-Cre) or whole-body disruption of H6pdh. Regeneration of [9,12,12-²H3]-cortisol (d3F) from [9,12,12-²H3]-cortisone (d3E), measuring 11βHSD1 reductase activity was assessed at steady state following infusion of [9,11,12,12-²H4]-cortisol (d4F) in male mice. Concentrations of steroids in plasma and amounts in liver, adipose tissue and brain were measured using mass spectrometry interfaced with matrix-assisted laser desorption ionisation or liquid chromatography. Amounts of d3F were higher in liver, compared with brain and adipose tissue. Rates of appearance of d3F were ~6-fold slower in H6pdh−/− mice, showing the importance for whole-body 11βHSD1 reductase activity. Disruption of liver 11βHSD1 reduced the amounts of d3F in liver (by ~36%), without changes elsewhere. In contrast disruption of 11βHSD1 in adipose tissue reduced rates of appearance of circulating d3F (by ~67%) and also reduced regenerated of d3F in liver and brain (both by ~30%). Thus, the contribution of hepatic 11βHSD1 to circulating glucocorticoid levels and amounts in other tissues is less than that of adipose tissue. [ABSTRACT FROM AUTHOR]

Summary: A 68‐year‐old man underwent elective surgical repair of an abdominal wall hernia under general anaesthesia. The operation required muscle relaxation, for which we used rocuronium. Following completion of surgery, 180 mg sugammadex was administered intravenously. Shortly afterwards, the patient became severely bradycardic with hypotension, refractory to treatment with ephedrine. This progressed to a pulseless electrical activity cardiac arrest. After 4 min of cardiopulmonary resuscitation, there was return of spontaneous circulation and, following a period of haemodynamic stability in which general anaesthesia was maintained, the patient emerged from anaesthesia without incident. He remained haemodynamically stable until discharge. Post‐resuscitation investigations including the serum tryptase level were unremarkable except for a mild respiratory acidosis and slightly elevated D‐dimers. Sugammadex‐induced bradycardia has previously been described, but its mechanism remains unknown. We believe that sugammadex was the cause of cardiac arrest in this case because of the timing and sequence of events, the evolution to pulseless electric activity and the relatively uneventful post‐arrest clinical course. We hope that our report will help to promote awareness about this potential complication of a now commonly‐used drug. [ABSTRACT FROM AUTHOR]

The iron(III)‐promoted synthesis of densely‐substituted 4H‐chalcogenchromene from organochalcogen propargylamines in the presence of diaryl dichalcogenides is reported. Subsequent C2‐functionalization with electrophiles and potassium trifluoroborate salts via Suzuki‐Miyaura coupling reaction are also presented. A plausible mechanism based on HRMS experiments is proposed and discussed. [ABSTRACT FROM AUTHOR]

Propolis can be an alternative to the use of ionophores in ruminants due to presence of compounds like flavonoids, fenolic acids, esters, fenolic aldehydes and ketones. In this study the impact of solid residue from alcoholic extraction of brown propolis (RBP) added to the diet for feedlot lambs on nutrients intake and digestibility, productive performance, body morphometric measures, carcass characteristics and meat fatty acid profile was determined. Twenty-four Texel × Suffolk crossbred castrated male lambs (19.83 ± 2.07 kg) were fed diet with 0 (negative control), 5, 10 g RBP per kg dry matter (DM) or monensin (positive control, 26 mg/kg DM), in total ration with roughage:concentrate ratio of 400:600 (w/w). RBP addition regardless used dose positively influenced (P < 0.05) productive performance parameters (final weight and daily weight gain). However, diet with 5 g RBP/kg DM lowered feed conversion ratio in comparison to negative control. Nutrient intake, digestibility of DM (684 g/kg), organic matter (701 g/kg) and fibre (695 g/kg) were similar among treatments. Live body length (78.89 cm), external carcass length (75.4 cm) and carcass compactness (0.253 kg/cm) also did not differ between groups. Moreover, diet supplementation with RBP did not affect hot and chilled carcass yields (451 and 447 g/kg, respectively). The addition of 5 g RBP/kg DM caused lower concentration of stearic acid (C18:0) and higher of oleic (C18:1n-9) and linoleic acids (C18:2n-6) in longissimus muscle of lambs in comparison to muscle from animals fed diet with monensin or control one. So, RBP can be used as nutritional additive to lamb feed to increase animal performance and modify meat fatty acid profile. [ABSTRACT FROM AUTHOR]

The synthesis of amidoglucals and glucal esters in good to high yields using 2-iodo-3,4,6-tri-O-acetyl-d-glucal as a substrate, Mo(CO)6 as a carbon monoxide source and PdCl2 as a catalyst is reported. This procedure shows advantages when compared to other published methodologies, as it is carried out in one pot relying on short reaction times at mild temperatures, under ligand-free conditions and with only one equivalent of Mo(CO)6. [ABSTRACT FROM AUTHOR]

Abstract: The discovery that pericytes are in vivo counterparts of Mesenchymal Stem/Stromal Cells (MSCs) has placed these perivascular cells in the research spotlight, bringing up hope for a well‐characterized cell source for clinical applications, alternative to poorly defined, heterogeneous MSCs preparations currently in use. Native pericytes express typical MSC markers and, after isolation by fluorescence‐activated cell sorting, display an MSC phenotype in culture. These features have been demonstrated in different species, including humans and horses, the main targets of regenerative treatments. Significant clinical potential of pericytes has been shown by transplantation of human cells into rodent models of tissue injury, and it is hoped that future studies will demonstrate clinical potential in veterinary species. Here, we provide an overview of the current knowledge on pericytes across different species including humans, companion and large animal models, in relation to their identification in different body tissues, methodology for prospective isolation, characterization, and potential for tissue regeneration. © 2017 International Society for Advancement of Cytometry [ABSTRACT FROM AUTHOR]

Previous evidence from in vitro studies suggests specific roles for a subset of miRNAs, including miR-21, miR-23a, miR-145, miR-503, miR-224, miR-383, miR-378, miR-132, and miR-212, in regulating ovarian follicle development. The objective of this study was to determine changes in the levels of these miRNAs in relation to follicle selection, maturation, and ovulation in the monovular equine ovary. In Experiment 1, follicular fluid was aspirated during ovulatory cycles from the dominant (DO) and largest subordinate (S) follicles of an ovulatory wave and the dominant (DA) follicle of a mid-cycle anovulatory wave (nZ6 mares). Follicular fluid levels of progesterone and estradiol were lower (P!0.01) in S follicles than in DO follicles, whereas mean levels of IGF1 were lower (P10.01) in S and DA follicles than in DO follicles. Relative to DO and DA follicles, S follicles had higher (P%0.01) follicular fluid levels of miR-145 and miR-378. In Experiment 2, follicular fluid and granulosa cells were aspirated from dominant follicles before (DO) and 24 h after (L) administration of an ovulatory dose of hCG (nZ5 mares/group). Relative to DO follicles, L follicles had higher follicular fluid levels of progesterone (PZ0.05) and lower granulosa cell levels of CYP19A1 and LHCGR (P!0.005). Levels of miR-21, miR-132, miR-212, and miR-224 were increased (P!0.05) in L follicles; thiswas associated with reduced expression of the putative miRNA targets, PTEN, RASA1, and SMAD4. These novel results may indicate a physiological involvement of miR-21, miR-145, miR-224, miR-378, miR-132, and miR-212 in the regulation of cell survival, steroidogenesis, and differentiation during follicle selection and ovulation in the monovular ovary. [ABSTRACT FROM AUTHOR]

A sensitive nanocalorimetric technology based on microcantilever sensors is presented. The technology, which combines very short response times with very small sample consumption, uses the bimetallic effect to detect thermal transitions. Specifically, abrupt variations in the Young's modulus and the thermal expansion coefficient produced by temperature changes have been employed to detect thermodynamic transitions. The technology has been used to determine the glass transition of poly(3-thiophene methyl acetate), a soluble semiconducting polymer with different nanotechnological applications. The glass transition temperature determined using microcantilevers coated with ultra-thin films of mass = 10-13 g is 5.2 °C higher than that obtained using a conventional differential scanning calorimeter for bulk powder samples of mass = 5 × 10-3 g. Atomistic molecular dynamics simulations on models that represent the bulk powder and the ultra-thin films have been carried out to provide understanding and rationalization of this feature. Simulations indicate that the film-air interface plays a crucial role in films with very small thickness, affecting both the organization of the molecular chains and the response of the molecules against the temperature. [ABSTRACT FROM AUTHOR]

Urreizti R, Moya-García AA, Pino- Ángeles A, Cozar M, Langkilde A, Fanhoe U, Esteves C, Arribas J, Vilaseca MA, Pérez-Dueñas B, Pineda M, González V, Artuch R, Baldellou, A, Vilarinho L, Fowler B, Ribes A, Sánchez-Jiménez F, Grinberg D, Balcells S. Molecular characterization of five patients with homocystinuria due to severe MTHFR deficiency. Methylenetetrahydrofolate reductase (MTHFR) plays a major role in folate metabolism. Disturbed function of the enzyme results in hyperhomocysteinemia and causes severe vascular and neurological disorders and developmental delay. Five patients suspected of having non-classical homocystinuria due to MTHFR deficiency were examined with respect to their symptoms, MTHFR enzyme activity and genotypes of the MTHFR gene. All patients presented symptoms of severe central nervous system disease. Two patients died, at the ages of 15 months and 14 years. One patient is currently 32 years old, and is being treated with betaine and folinic acid. The other two patients, with an early diagnosis and a severe course of the disease, are currently improving under treatment. MTHFR enzyme activity in the fibroblasts of four of the patients was practically undetectable. We found four novel mutations, three of which were missense changes c.664G> T (p.V218L), c.1316T> C (p.F435S) and c.1733T> G (p.V574G), and the fourth was the 1-bp deletion c.1780delC (p.L590CfsX72). We also found the previously reported nonsense mutation c.1420G> T (p.E470X). All the patients were homozygous. Molecular modelling of the double mutant allele (p.V218L; p.A222V) revealed that affinity for FAD was not affected in this mutant. For the p.E470X mutation, the evidence pointed to nonsense-mediated mRNA decay. In general, genotype-phenotype analysis predicts milder outcomes for patients with missense changes than for those in which mutations led to severe alterations of the MTHFR protein. [ABSTRACT FROM AUTHOR]

In spite of the worldwide occurrence of domestic cats and dogs, and their close relationship with humans, the number of published papers on free-ranging cats Felis catus and dogs Canis familiaris, is small. The diet of both species was estimated in a suburban and rural environment in July 2002 and January 2003. Visual observations and scat collection of both species were accomplished along a 10 km transect line in the Campus ‘Luiz de Queiroz’, University of São Paulo, Piracicaba, south-eastern Brazil. The diet of both species was determined by analysis of sterilized, washed, dried and sorted scats. Estimated abundances of free-ranging cats and dogs in the sampled area were 81 (±4.32) and 42 (±2.96), respectively. Cats and dogs were more abundant in the suburban than in the rural environment ( t=3.78, P<0.001, N=55; t=8.38, P<0.001, N=55, respectively) and cats were more abundant than dogs in the suburban environment ( t=6.76, P<0.001, N=55), even though there was no significant difference between the abundance of both species in the rural environment ( t=0.82, P=0.46, N=55). Invertebrates were the most commonly consumed item by both species, followed by mammals (cats: 63.24 and 20.51%; dogs: 57.05 and 25.15%, respectively). Niche breadth was 0.4892 for cats and 0.4463 for dogs. Niche overlap was almost complete (0.97108). The consumption of mammals was estimated to be between 16.76 and 25.42 kg individual−1year−1 for dogs and between 2.01 and 2.9 kg individual−1year−1 for cats. These data might be useful to establish a management program to minimize the predation pressure of free-ranging cats and dogs on wildlife. [ABSTRACT FROM AUTHOR]

We report our experience with the use of covered stents for the management of coarctation of the aorta. From December 2001 to March 2004, nine patients (seven males: median age, 31 years; mean weight, 65 ± 15 kg) underwent implantation. Indications included critical or atretic native coarctation (n = 4), patients > 50 years of age (n = 2), associated patent ductus arleriosus (n = 1) or adjacent aneurysm (n = 1), and the presence of a circumferential fracture within a previously implanted stent (n = 1). The covered balloon-expandable Cheatham-Platinum stem and the self-expandable stent graft Braile were employed. Adequate implantation was observed in all patients. Gradients were reduced from 54 ± 14 to 3 ± 8 mmHg and the coarctation site increased from 2.4 ± 2.9 to 15.9 ± 4.3 mm. The patent ductus arteriosus was immediately closed and the aneurysm excluded. Two patients > 35 years with aneurysmal ascending aorta and metallic aortic prosthesis had aneurysm formation at follow-up. with one undergoing aneurysm exclusion using a Braile stent. Although covered stents are useful in the management of selected patients with coarctation, aneurysm formation may still occur in patients with markers of aortic wall weakness. Refinements in the deployment technique and/or the stent design are needed to eliminate this risk. [ABSTRACT FROM AUTHOR]

What's already known about this topic?Chromothripsis is a recently described phenomenon whereby a single catastrophic event leads to multiple chromosome breaks and subsequent repair through nonhomologous end joining. The result can present karyotypically as a complex rearrangement and occurs both congenitally and in cancer cells. What does this study add?We report, to our knowledge, the first case of congenital chromothripsis uncovered prenatally through a combination of G ‐ banded karyotype analysis and whole ‐ genome sequencing by jumping libraries. The G ‐ banded karyotype initially suggested the involvement of five chromosomes and six breakpoints. Whole ‐ genome sequencing further resolved this event to include nine total breakpoints that disrupt seven independent genes, all in the presence of a normal microarray result. This emphasizes the complementarity that whole ‐ genome sequencing can provide to the initial karyotype analysis as a reflex test when a rearrangement is detected. We also discuss the dilemma of prognosis with this finding. [ABSTRACT FROM AUTHOR]

The melting transition of a model semicrystalline polymer has been detected by the microcantilever deflection as a function of temperature. Deflection measurements were done on arrays of 8-cantilevers spin coated with the semicrystalline polymer: poly (propylene azelate). The melting of the polymer has been corroborated by grazing incidence wide angle x-ray scattering experiments performed with synchrotron radiation over a single cantilever. [ABSTRACT FROM AUTHOR]

In this work, crater formation by single 20 MeV Au ions on ultra-thin poly(methyl methacrylate) (PMMA) films was systematically investigated as a function of the thickness t of the layers (2 nm< t <100 nm). The samples were bombarded at grazing angles of incidence (79°and 84° to the surface normal) and morphological changes analyzed employing scanning force microscopy in the tapping mode. For thicknesses from 100 nm down to approximately 20 nm no major changes were observed in the size and morphology of the impact features. For t<20 nm rims (hillocks) start to diminish, but crater hole size showed very little changes even for very thin samples of ∼ 8 nm. Similar results were observed for both impact angles. The results indicate a different depth of origin for crater and ridge formation due to a fast ion impact. (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]