Yeasts Have Evolved Divergent Enzyme Strategies To Deconstruct and Metabolize Xylan

Together with bacteria and filamentous fungi, yeasts actively take part in the global carbon cycle. Over 100 yeast species have been shown to grow on the major plant polysaccharide xylan, which requires an arsenal of carbohydrate active enzymes. However, which enzymatic strategies yeasts use to deconstruct xylan and what specific biological roles they play in its conversion remain unclear. In fact, genome analyses reveal that many xylan-metabolizing yeasts lack expected xylanolytic enzymes. Guided by bioinformatics, we have here selected three xylan-metabolizing ascomycetous yeasts for in-depth characterization of growth behavior and xylanolytic enzymes. The savanna soil yeast Blastobotrys mokoenaii displays superior growth on xylan thanks to an efficient secreted glycoside hydrolase family 11 (GH11) xylanase; solving its crystal structure revealed a high similarity to xylanases from filamentous fungi. The termite gut-associated Scheffersomyces lignosus, in contrast grows more slowly, and its xylanase activity was found to be mainly cell surface-associated. The wood-isolated Wickerhamomyces canadensis, surprisingly, could not utilize xylan as the sole carbon source without the addition of xylooligosaccharides or exogenous xylanases or even co-culturing with B. mokoenaii, suggesting that W. canadensis relies on initial xylan hydrolysis by neighboring cells. Furthermore, our characterization of a novel W. canadensis GH5 subfamily 49 (GH5_49) xylanase represents the first demonstrated activity in this subfamily. Our collective results provide new information on the variable xylanolytic systems evolved by yeasts and their potential roles in natural carbohydrate conversion. IMPORTANCE Microbes that take part in the degradation of the polysaccharide xylan, the major hemicellulose component in plant biomass, are equipped with specialized enzyme machineries to hydrolyze the polymer into monosaccharides for further metabolism. However, despite being found in virtually every habitat, little is known of how yeasts break down and metabolize xylan and what biological role they may play in its turnover in nature. Here, we have explored the enzymatic xylan deconstruction strategies of three underexplored yeasts from diverse environments, Blastobotrys mokoenaii from soil, Scheffersomyces lignosus from insect guts, and Wickerhamomyces canadensis from trees, and we show that each species has a distinct behavior regarding xylan conversion. These findings may be of high relevance for future design and development of microbial cell factories and biorefineries utilizing renewable plant biomass

Tomosynthesis in pulmonary cystic fibrosis with comparison to radiography and computed tomography: a pictorial review

The purpose of this pictorial review is to illustrate chest imaging findings of cystic fibrosis (CF) using tomosynthesis (digital tomography), in comparison to radiography and computed tomography (CT). CF is a chronic systemic disease where imaging has long been used for monitoring chest status. CT exposes the patient to a substantially higher radiation dose than radiography, rendering it unsuitable for the often needed repeated examinations of these patients. Tomosynthesis has recently appeared as an interesting low dose alternative to CT, with an effective dose of approximately 0.08 mSv for children and 0.12 mSv for adults. Tomosynthesis is performed on the same X-ray system as radiography, adding only about 1 min to the normal examination time. Typical pulmonary changes in CF such as mucus plugging, bronchial wall thickening, and bronchiectases are shown in significantly better detail with tomosynthesis than with traditional radiography. In addition, the cost for a tomosynthesis examination is low compared to CT. To reduce the radiation burden of patients with CF it is important to consider low dose alternatives to CT, especially in the paediatric population. Tomosynthesis has a lower radiation dose than CT and gives a superior visualisation of pulmonary CF changes compared to radiography. It is important to further determine the role of tomosynthesis for monitoring disease progression in CF

The role of 'confounding by indication' in assessing the effect of quality of care on disease outcomes in general practice: results of a case-control study.

BACKGROUND: In quality of care research, limited information is found on the relationship between quality of care and disease outcomes. This case-control study was conducted with the aim to assess the effect of guideline adherence for stroke prevention on the occurrence of stroke in general practice. We report on the problems related to a variant of confounding by indication, that may be common in quality of care studies. METHODS: Stroke patients (cases) and controls were recruited from the general practitioner's (GP) patient register, and an expert panel assessed the quality of care of cases and controls using guideline-based review criteria. RESULTS: A total of 86 patients was assessed. Compared to patients without shortcomings in preventive care, patients who received sub-optimal care appeared to have a lower risk of experiencing a stroke (OR 0.60; 95% CI 0.24 to 1.53). This result was partly explained by the presenc

Suboptimal asthma care for immigrant children: results of an audit study

<p>Abstract</p> <p>Background</p> <p>Little is known on the scope and nature of ethnic inequalities in suboptimal asthma care for children. This study aimed to assess (1) ethnic differences in suboptimal asthma care for children with an asthma exacerbation who consulted a physician, and (2) ethnic differences in the nature of suboptimal care.</p> <p>Methods</p> <p>All children aged 6–16 years who during a period of six months consulted the paediatric department of the Academic Medical Centre-University of Amsterdam or one of the six regional primary care centres with an asthma exacerbation were included. Clinical guidelines were systematically converted to review criteria following the strategy as proposed by the Agency for Health Care Policy and Research. Based upon these review criteria and their experience experts of two multidisciplinary panels retrospectively assessed the quality of care and its (possible) failure to prevent the occurrence of asthma exacerbation.</p> <p>Results</p> <p>Only a small number of children (n = 35) were included in the analysis as a result of which the ethnic differences in suboptimal care were not significant. However, the results do indicate immigrant children, in particular 'other non-Western' children (n = 11), more frequently to receive suboptimal care related to the asthma exacerbation when compared to ethnic Dutch children. Furthermore, we found the nature of suboptimal care to differ with under-prescribing in the 'other non-Western' group (n = 11), lack of information exchange between physicians in the Surinamese/Antillean group (n = 12) and lack of education, and counselling of patients and parents in the ethnic Dutch (n = 12) as the most relevant factor.</p> <p>Conclusion</p> <p>Ethnic inequalities in the scope and nature of suboptimal asthma care for children in the Netherlands seem to exist. For the non-western immigrant groups the results indicate the importance of the prescription behaviour of the medical doctor, as well as the supervision by one health care provider.</p

Electron Transfer from Cyt b559 and Tyrosine-D to the S2 and S3 states of the water oxidizing complex in Photosystem II at Cryogenic Temperatures

The Mn4CaO5 cluster of photosystem II (PSII) catalyzes the oxidation of water to molecular oxygen through the light-driven redox S-cycle. The water oxidizing complex (WOC) forms a triad with Tyrosine(Z) and P-680, which mediates electrons from water towards the acceptor side of PSII. Under certain conditions two other redox-active components, Tyrosine(D) (Y-D) and Cytochrome b (559) (Cyt b (559)) can also interact with the S-states. In the present work we investigate the electron transfer from Cyt b (559) and Y-D to the S-2 and S-3 states at 195 K. First, Y-D (aEuro cent) and Cyt b (559) were chemically reduced. The S-2 and S-3 states were then achieved by application of one or two laser flashes, respectively, on samples stabilized in the S-1 state. EPR signals of the WOC (the S-2-state multiline signal, ML-S-2), Y-D (aEuro cent) and oxidized Cyt b (559) were simultaneously detected during a prolonged dark incubation at 195 K. During 163 days of incubation a large fraction of the S-2 population decayed to S-1 in the S-2 samples by following a single exponential decay. Differently, S-3 samples showed an initial increase in the ML-S-2 intensity (due to S-3 to S-2 conversion) and a subsequent slow decay due to S-2 to S-1 conversion. In both cases, only a minor oxidation of Y-D was observed. In contrast, the signal intensity of the oxidized Cyt b (559) showed a two-fold increase in both the S-2 and S-3 samples. The electron donation from Cyt b (559) was much more efficient to the S-2 state than to the S-3 state

An electrogenic redox loop in sulfate reduction reveals a likely widespread mechanism of energy conservation

The bioenergetics of anaerobic metabolism frequently relies on redox loops performed by membrane complexes with substrate- and quinone-binding sites on opposite sides of the membrane. However, in sulfate respiration (a key process in the biogeochemical sulfur cycle), the substrate- and quinone-binding sites of the QrcABCD complex are periplasmic, and their role in energy conservation has not been elucidated. Here we show that the QrcABCD complex of Desulfovibrio vulgaris is electrogenic, as protons and electrons required for quinone reduction are extracted from opposite sides of the membrane, with a H+/e− ratio of 1. Although the complex does not act as a H+-pump, QrcD may include a conserved proton channel leading from the N-side to the P-side menaquinone pocket. Our work provides evidence of how energy is conserved during dissimilatory sulfate reduction, and suggests mechanisms behind the functions of related bacterial respiratory complexes in other bioenergetic contexts

The Artelon CMC spacer compared with tendon interposition arthroplasty: A randomized, controlled, multicenter study of 109 patients with osteoarthritis followed for 1 year

Background and purpose The Artelon CMC spacer is designed for surgical treatment of osteoarthritis (OA) in the carpometacarpal joint of the thumb (CMC-I). Good results using this degradable device were previously presented in a pilot study. We now present results from a larger randomized, controlled, multicenter study

Monoamine related functional gene variants and relationships to monoamine metabolite concentrations in CSF of healthy volunteers

BACKGROUND: Concentrations of monoamine metabolites in human cerebrospinal fluid (CSF) have been used extensively as indirect estimates of monoamine turnover in the brain. CSF monoamine metabolite concentrations are partly determined by genetic influences. METHODS: We investigated possible relationships between DNA polymorphisms in the serotonin 2C receptor (HTR2C), the serotonin 3A receptor (HTR3A), the dopamine D(4 )receptor (DRD4), and the dopamine β-hydroxylase (DBH) genes and CSF concentrations of 5-hydroxyindolacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) in healthy volunteers (n = 90). RESULTS: The HTR3A 178 C/T variant was associated with 5-HIAA levels (p = 0.02). The DBH-1021 heterozygote genotype was associated with 5-HIAA (p = 0.0005) and HVA (p = 0.009) concentrations. Neither the HTR2C Cys23Ser variant, nor the DRD4 -521 C/T variant were significantly associated with any of the monoamine metabolites. CONCLUSIONS: The present results suggest that the HTR3A and DBH genes may participate in the regulation of dopamine and serotonin turnover rates in the central nervous system