In Silico Evidence for Gluconeogenesis from Fatty Acids in Humans

The question whether fatty acids can be converted into glucose in humans has a long standing tradition in biochemistry, and the expected answer is “No”. Using recent advances in Systems Biology in the form of large-scale metabolic reconstructions, we reassessed this question by performing a global investigation of a genome-scale human metabolic network, which had been reconstructed on the basis of experimental results. By elementary flux pattern analysis, we found numerous pathways on which gluconeogenesis from fatty acids is feasible in humans. On these pathways, four moles of acetyl-CoA are converted into one mole of glucose and two moles of CO2. Analyzing the detected pathways in detail we found that their energetic requirements potentially limit their capacity. This study has many other biochemical implications: effect of starvation, sports physiology, practically carbohydrate-free diets of inuit, as well as survival of hibernating animals and embryos of egg-laying animals. Moreover, the energetic loss associated to the usage of gluconeogenesis from fatty acids can help explain the efficiency of carbohydrate reduced and ketogenic diets such as the Atkins diet

Predicting site index from climate and soil variables for cork oak (Quercus suber L.) stands in Portugal

Site productivity, assessed through site index, was modelled using partial least squares regression as a function of soil and climatic variables. Two alternative models were developed: a full model, considering all available explanatory variables, and a reduced model, considering only variables that can be obtained without digging a soil pit. The reduced model was used for mapping the site index distribution in Portugal, on the basis of existing digital cartography available for the whole country. The developed models indicate the importance of water availability and soil water holding capacity for site index value distribution. Site index was related to climate, namely evaporation and frost, and soil characteristics such as lithology, soil texture, soil depth, thickness of the A horizon and soil classification. The variability of the estimated values within the map (9.5–16.8 m with an average value of 13.4 m) reflects the impact of soil characteristics on the site productivity estimation. These variables should be taken into consideration during the establishment of new plantations of cork oak, and management of existing plantations. Results confirm the potential distribution of cork oak in coastal regions. They also suggest the existence of a considerable area, located both North and South of the Tagus river, where site indices values of medium (]13;15]) to high (]15;17]) productivity classes may be expected. The species is then expected to be able to have good productivity along the northern coastal areas of Portugal, where presently it is not a common species but where, according to historical records, it occurred until the middle of the sixteenth century. The present research focused on tree growth. Cork growth and cork quality distribution needs to be further researched through the establishment of long term experimental sites along the distribution area of cork oak, namely in the central and northern coastal areas of the countryinfo:eu-repo/semantics/publishedVersio

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Niche definition and guidance for detailed niche evaluation

With interest we read the correspondence of Bamberg et al.1 and Scioscia et al.2 about the randomized controlled trial of the first authors concerning the uterine niche after caesarean section (CS).3 They state that at the time of the trial it was not established which technique should be used in the evaluation of a caesarean scar or niche in daily practice and future research. Both authors underline the need for a uniform evaluation of the CS scar establishing an internationally accepted definition of a niche. In their study a niche was defined as an anechogenic area at the site of the uterine scar with a depth of at least 1 mm

Definition and sonographic reporting system for Cesarean scar pregnancy in early gestation: modified Delphi method

Objective To develop a standardized sonographic evaluation and reporting system for Cesarean scar pregnancy (CSP) in the first trimester, for use by both general gynecology and expert clinics. Methods A modified Delphi procedure was carried out, in which 28 international experts in obstetric and gynecological ultrasonography were invited to participate. Extensive experience in the use of ultrasound to evaluate Cesarean section (CS) scars in early pregnancy and/or publications concerning CSP or niche evaluation was required to participate. Relevant items for the detection and evaluation of CSP were determined based on the results of a literature search. Consensus was predefined as a level of agreement of at least 70% for each item, and a minimum of three Delphi rounds were planned (two online questionnaires and one group meeting). Results Sixteen experts participated in the Delphi study and four Delphi rounds were performed. In total, 58 items were determined to be relevant. We differentiated between basic measurements to be performed in general practice and advanced measurements for expert centers or for research purposes. The panel also formulated advice on indications for referral to an expert clinic. Consensus was reached for all 58 items on the definition, terminology, relevant items for evaluation and reporting of CSP. It was recommended that the first CS scar evaluation to determine the location of the pregnancy should be performed at 6–7 weeks' gestation using transvaginal ultrasound. The use of magnetic resonance imaging was not considered to add value in the diagnosis of CSP. A CSP was defined as a pregnancy with implantation in, or in close contact with, the niche. The experts agreed that a CSP can occur only when a niche is present and not in relation to a healed CS scar. Relevant sonographic items to record included gestational sac (GS) size, vascularity, location in relation to the uterine vessels, thickness of the residual myometrium and location of the pregnancy in relation to the uterine cavity and serosa. According to its location, a CSP can be classified as: (1) CSP in which the largest part of the GS protrudes towards the uterine cavity; (2) CSP in which the largest part of the GS is embedded in the myometrium but does not cross the serosal contour; and (3) CSP in which the GS is partially located beyond the outer contour of the cervix or uterus. The type of CSP may change with advancing gestation. Future studies are needed to validate this reporting system and the value of the different CSP types. Conclusion Consensus was achieved among experts regarding the sonographic evaluation and reporting of CSP in the first trimester. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology

A practical guideline for examining a uterine niche using ultrasonography in non-pregnant women: a modified Delphi method amongst European experts

To generate a uniform, internationally recognized guideline for detailed uterine niche evaluation by ultrasonography in non-pregnant women using a modified Delphi method amongst international experts.status: publishe

Sonographic examination of uterine niche in non-pregnant women: a modified Delphi procedure

Objective To generate guidance for detailed uterine niche evaluation by ultrasonography in the non‐pregnant woman, using a modified Delphi procedure amongst European experts. Methods Twenty gynecological experts were approached through their membership of the European Niche Taskforce. All experts were physicians with extensive experience in niche evaluation in clinical practice and/or authors of niche publications. By means of a modified Delphi procedure, relevant items for niche measurement were determined based on the results of a literature search and recommendations of a focus group of six Dutch experts. It was predetermined that at least three Delphi rounds would be performed (two online questionnaires completed by the expert panel and one group meeting). For it to be declared that consensus had been reached, a consensus rate for each item of at least 70% was predefined. Results Fifteen experts participated in the Delphi procedure. Consensus was reached for all 42 items on niche evaluation, including definitions, relevance, method of measurement and tips for visualization of the niche. A niche was defined as an indentation at the site of a Cesarean section with a depth of at least 2 mm. Basic measurements, including niche length and depth, residual and adjacent myometrial thickness in the sagittal plane, and niche width in the transverse plane, were considered to be essential. If present, branches should be reported and additional measurements should be made. The use of gel or saline contrast sonography was preferred over standard transvaginal sonography but was not considered mandatory if intrauterine fluid was present. Variation in pressure generated by the transvaginal probe can facilitate imaging, and Doppler imaging can be used to differentiate between a niche and other uterine abnormalities, but neither was considered mandatory. Conclusion Consensus between niche experts was achieved regarding ultrasonographic niche evaluation. © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology