Critical role of metals in biochemical properties of xylose isomerase

Improving the activity of xylose isomerase (XI) is highly desired for achieving efficient fermentation of xylose in lignocellulosic biomass using XI-expressing S. cerevisiae. XI is a metalloenzyme which requires two bivalent metals for its catalytic activity. The enzyme from Piromyces sp. E2 (PirXI)[1],[2] is activated with various metal ions including Mg2+, Mn2+, Ca2+, Co2+, Zn2+ and Fe2+. The biochemical properties of PirXI are dependent on the types of its metal cofactors. Moreover, the enzyme shows different affinities towards these metals. Characterization of these properties is critical for understanding the enzyme behavior in vivo and to further adapt the enzyme to the cytosolic metal environment. Recently, we have shown that altered intracellular metal composition can improve anaerobic growth of a xylose-fermenting strain by enhancing the activity of PirXI[3]. Furthermore, our current study on PirXI and other studies on different XIs have shown that it is also possible to change the metal preferences of the enzyme[4]. A PirXI variant with a single amino acid substitution in the proximity of the metal binding residues showed significant changes in metal preference compared to the wild-type PirXI. Further exploration on metal specificity of PirXI is necessary to optimize the in vivo enzyme activity. References: 1.Kuyper M, Harhangi HR, Stave AK, Winkler AA, Jetten MS, de Laat WT, den Ridder JJ, Op den Camp HJ, van Dijken JP, Pronk JT, FEMS Yeast Research 4 (2003) 69-78 2.van Maris AJ, Winkler AA, Kuyper M, de Laat WT, van Dijken JP, Pronk JT, Adv Biochem Engin/Biotechnol (2007) 108: 179–204 3.Verhoeven MD, Lee M, Kamoen L, van den Broek M, Janssen DB, Daran JG, van Maris AJA, Pronk JT, Sci. Rep (2017) 7, 46155 4.van Tilbeurgh H, Jenkins J, Chiadmi M, Janin J, Wodak SJ, Mrabet NT, Lambeir AM, Biochemistry (1992) 31: 5467-547

The effective dose due to scattered radiation at patients during primary osteosynthesis; a multicenter prospective observational study

Objectives: During osteosynthesis of a fracture patients are exposed to the primary radiation of an X-ray image and scattered (secondary) radiation. The primary objective was to measure the amount of scattered radiation at the thyroid, breast tissue, and gonads of patients undergoing primary osteosynthesis of acute fractures. The secondary objective was to calculate the effective dose caused by scattered radiation. Methods: In this multicenter prospective observational case series patients undergoing a primary osteosynthesis of an acute fracture of hand/wrist, shoulder, ankle, knee, or hip were included. Three dosimeters were attached to the patient at the level of the thyroid, breast and gonads. Scattered radiation doses were corrected for the average background radiation per hospital per day. Results: A total of 205 patients were included between March 6, 2017 and June 18, 2018; 49 (24%) had a hand/wrist fracture, 37 (18%) a shoulder fracture, 47 (23%) an ankle fracture, 35 (17%) a knee fracture, and 37 (18%) a hip fracture. In 32–39% of all patients undergoing primary osteosynthesis effective scattered doses was detected. The highest measured median effective dose was 60.43 µSv (P25–P75 33.84–100.76) at the gonads during hip osteosynthesis. Conclusions: The results of this study show that scattered radiation is detectable in a third of patients undergoing an osteosynthesis. However, both effective doses due to direct radiation and scattered radiation are low. Advances in knowledge: This is the first study that presents that no radiation protection for patients undergoing an osteosynthesis is necessary

HLA-DR expression on monocytes and systemic inflammation in patients with ruptured abdominal aortic aneurysms

INTRODUCTION: Mortality from ruptured abdominal aortic aneurysms (RAAA) remains high. Severe systemic inflammation, leading to multi-organ failure, often occurs in these patients. In this study we describe the level of HLA-DR expression in a consecutive group of patients following surgery for RAAA and compare results between survivors and non-survivors. A similar comparison is made for IL-6 and IL-10 levels and Sequential Organ Failure Assessment (SOFA) scores. METHODS: This is a prospective observational study. Patients with RAAA were prospectively analysed. Blood samples were collected on days 1, 3, 5, 7, 10 and 14. The fraction of CD-14 positive monocytes expressing HLA-DR was measured by flow-cytometry. IL-6 and IL-10 levels were measured by ELISA. RESULTS: The study included 30 patients with a median age of 70 years, of which 27 (90%) were men. Six patients died from multiple organ failure, all other patients survived. The SOFA scores were significantly higher in non-survivors on days 1 through 14. HLA-DR expression on monocytes was significantly lower on days 3, 5, 7, 10 and 14 in non-survivors. IL-6 and IL-10 levels were significantly higher in non-survivors on day 1 and days 1 and 3, respectively. CONCLUSION: HLA-DR expression on monocytes was decreased, especially in non-survivors. All patients with RAAA displayed a severe inflammatory and anti-inflammatory response with an increased production of IL-6 and IL-10. Poor outcome is associated with high levels of IL-6 and IL-10 and a high SOFA score in the first three days after surgery, while low levels of HLA-DR expression are observed from day three after RAAA repair

Spring migration of Black-tailed Godwits in Iberia 2014:Mission Report Sado, Tejo and Extremadura

In 2004 the University of Groningen has started a long-term demographic project on a partly colour-ringed breeding population of Black-tailed Godwits Limosa limosa in SW Friesland, The Netherlands(read more on http://www.rug.nl/research/animal-ecology/research/piersma-lab/meadow-birds).From half December onwards, Black-tailed Godwits leave their wintering areas in West-Africa to theirstopover areas in southern Iberia. Here they are confined to three main areas: Doñana NP andExtremadura in Spain and the rice fields surrounding the Tejo and Sado estuaries near Lisbon inPortugal. Resighting color marked birds during the stopover period is necessary for several reasons.Firstly, if a godwit disperses outside our study area, the chance that it will be resighted elsewhere inThe Netherlands is small. Without the resightings in the stopover area, we would assume that thisindividual is dead and therefore underestimate annual survival. Secondly, with enough resightings inthe Iberian Peninsula we can calculate seasonal survival. In other words, we can calculate in whichperiod mortalities occur more often. Thirdly, by measuring the density of individuals with colourmarks, we can monitor the population size of the western European part of the Black-tailed Godwitpopulation. Below you will find a summary and detailed day-to-day trip report of our work inPortugal and Extremadura in 2014

A randomized controlled trial of three years growth hormone and gonadotropin-releasing hormone agonist treatment in children with idiopathic short stature and intrauterine growth retardation

We assessed the effectiveness and safety of 3 yr combined GH and GnRH agonist (GnRHa) treatment in a randomized controlled study in children with idiopathic short stature (ISS) or intrauterine growth retardation (IUGR). Gonadal suppression, GH reserve, and adrenal development were assessed by hormone measurements in both treated children and controls during the study period. Thirty-six short children, 24 girls (16 ISS/8 IUGR) and 12 boys (8 ISS/4 IUGR), with a height SD score of -2 SD or less in early puberty (girls, B2-3; boys, G2-3), were randomly assigned to treatment (n = 18) with GH (genotropin 4 IU/m(2). day) and GnRHa (triptorelin, 3.75 mg/28 days) or no treatment (n = 18). At the start of the study mean (SD) age was 11.4 (0.56) or 12.2 (1.12) yr whereas bone age was 10.7 (0.87) or 10.9 (0.63) yrs in girls and boys, respectively. During 3 yr of study height SD score for chronological age did not change in both treated children and controls, whereas a decreased rate of bone maturation after treatment was observed [mean (SD) 0.55 (0.21) 'yr'/yr vs. 1.15 (0.37) 'yr'/yr in controls, P < 0.001, girls and boys together]. Height SD score for bone age and predicted adult height increased significantly after 3 yr of treatment; compared with controls the predicted adult height gain was 8.0 cm in girls and 10.4 cm in boys. Furthermore, the ratio between sitting height/height SD score decreased significantly in treated children, whereas body mass index was not influenced by treatment. Puberty was effectively arrested in the treated children, as was confirmed by physical examination and prepubertal testosterone and estradiol levels. GH-dependent hormones including serum insulin-like growth factor I and II, carboxy terminal propeptide of type I collagen, amino terminal propeptide of type III collagen, alkaline phosphatase, and osteocalcin were not different between treated children and controls during the study period. Thus, a GH dose of 4 IU/m(2) seems adequate for stabilization of the GH reserve and growth in these GnRHa-treated children. We conclude that 3 yr treatment with GnRHa was effective in suppressing pubertal development and skeletal maturation, whereas the addition of GH preserved growth velocity during treatment. This resulted in a considerable gain in predicted adult height, without demonstrable side effects. Final height results will provide the definite answer on the effectiveness of this combined treatment

Development of refractive errors - what can we learn from inherited retinal dystrophies?

PURPOSE: It is unknown which retinal cells are involved in the retina-to-sclera signaling cascade causing myopia. As inherited retinal dystrophies (IRD) are characterized by dysfunction of a single retinal cell type and have a high risk of refractive errors, a study investigating the affected cell type, causal gene and refractive error in IRDs may provide insight herein. DESIGN: Case-control study. METHODS: _Study population:_ 302 patients with IRD from two ophthalmogenetic centers in the Netherlands. _Reference population:_ population-based Rotterdam Study-III and ERF Study (N=5,550). Distributions and mean spherical equivalent (SE) were calculated for main affected cell type and causal gene; and risks of myopia and hyperopia were evaluated using logistic regression. RESULTS: Bipolar cell related dystrophies were associated with the highest risk of SE high myopia 239.7; OR mild hyperopia 263.2, both P<0.0001; SE -6.86 D [SD 6.38]); followed by cone dominated dystrophies (OR high myopia 19.5, P<0.0001; OR high hyperopia 10.7, P=0.033; SE -3.10 D [SD 4.49]); rod dominated dystrophies (OR high myopia 10.1, P<0.0001; OR high hyperopia 9.7, P=0.001; SE -2.27 D [SD 4.65]); and RPE related dystrophies (OR low myopia 2.7; P=0.001; OR high hyperopia 5.8; P=0.025; SE -0.10 D [SD 3.09]). Mutations in RPGR (SE -7.63 D [SD 3.31]) and CACNA1F (SE -5.33 D [SD 3.10]) coincided with the highest degree of myopia; in CABP4 (SE 4.81 D [SD 0.35]) with the highest degree of hyperopia. CONCLUSIONS: Refractive errors, in particular myopia, are common in IRD. The bipolar synapse, and the inner and outer segments of the photoreceptor may serve as critical sites for myopia development