Signatures of arithmetic simplicity in metabolic network architecture

Metabolic networks perform some of the most fundamental functions in living cells, including energy transduction and building block biosynthesis. While these are the best characterized networks in living systems, understanding their evolutionary history and complex wiring constitutes one of the most fascinating open questions in biology, intimately related to the enigma of life's origin itself. Is the evolution of metabolism subject to general principles, beyond the unpredictable accumulation of multiple historical accidents? Here we search for such principles by applying to an artificial chemical universe some of the methodologies developed for the study of genome scale models of cellular metabolism. In particular, we use metabolic flux constraint-based models to exhaustively search for artificial chemistry pathways that can optimally perform an array of elementary metabolic functions. Despite the simplicity of the model employed, we find that the ensuing pathways display a surprisingly rich set of properties, including the existence of autocatalytic cycles and hierarchical modules, the appearance of universally preferable metabolites and reactions, and a logarithmic trend of pathway length as a function of input/output molecule size. Some of these properties can be derived analytically, borrowing methods previously used in cryptography. In addition, by mapping biochemical networks onto a simplified carbon atom reaction backbone, we find that several of the properties predicted by the artificial chemistry model hold for real metabolic networks. These findings suggest that optimality principles and arithmetic simplicity might lie beneath some aspects of biochemical complexity

Cross-Dimensional Mapping of Number, Length and Brightness by Preschool Children

Human adults in diverse cultures, children, infants, and non-human primates relate number to space, but it is not clear whether this ability reflects a specific and privileged number-space mapping. To investigate this possibility, we tested preschool children in matching tasks where the dimensions of number and length were mapped both to one another and to a third dimension, brightness. Children detected variation on all three dimensions, and they reliably performed mappings between number and length, and partially between brightness and length, but not between number and brightness. Moreover, children showed reliably better mapping of number onto the dimension of length than onto the dimension of brightness. These findings suggest that number establishes a privileged mapping with the dimension of length, and that other dimensions, including brightness, can be mapped onto length, although less efficiently. Children's adeptness at number-length mappings suggests that these two dimensions are intuitively related by the end of the preschool years

High glycine concentration increases collagen synthesis by articular chondrocytes in vitro: acute glycine deficiency could be an important cause of osteoarthritis

Collagen synthesis is severely diminished in osteoarthritis; thus, enhancing it may help the regeneration of cartilage. This requires large amounts of glycine, proline and lysine. Previous works of our group have shown that glycine is an essential amino acid, which must be present in the diet in large amounts to satisfy the demands for collagen synthesis. Other authors have shown that proline is conditionally essential. In this work we studied the effect of these amino acids on type II collagen synthesis. Bovine articular chondrocytes were cultured under a wide range of different concentrations of glycine, proline and lysine. Chondrocytes were characterized by type II collagen immunocytochemistry of confluence monolayer cultures. Cell growth and viability were assayed by trypan blue dye exclusion method. Type II collagen was measured in the monolayer, every 48 h for 15 days by ELISA. Increase in concentrations of proline and lysine in the culture medium enhances the synthesis of type II collagen at low concentrations, but these effects decay before 1.0 mM. Increase of glycine as of 1.0 mM exceeds these effects and this increase continues more persistently by 60–75%. Since the large effects produced by proline and lysine are within the physiological range, while the effect of glycine corresponds to a much higher range, these results demonstrated a severe glycine deficiency for collagen synthesis. Thus, increasing glycine in the diet may well be a strategy for helping cartilage regeneration by enhancing collagen synthesis, which could contribute to the treatment and prevention of osteoarthriti

Scientific merits and analytical challenges of tree-ring densitometry

R.W. was supported by NERC grant NE/K003097/1.X-ray microdensitometry on annually-resolved tree-ring samples has gained an exceptional position in last-millennium paleoclimatology through the maximum latewood density parameter (MXD), but also increasingly through other density parameters. For fifty years, X-ray based measurement techniques have been the de facto standard. However, studies report offsets in the mean levels for MXD measurements derived from different laboratories, indicating challenges of accuracy and precision. Moreover, reflected visible light-based techniques are becoming increasingly popular and wood anatomical techniques are emerging as a potentially powerful pathway to extract density information at the highest resolution. Here we review the current understanding and merits of wood density for tree-ring research, associated microdensitometric techniques, and analytical measurement challenges. The review is further complemented with a careful comparison of new measurements derived at 17 laboratories, using several different techniques. The new experiment allowed us to corroborate and refresh ?long-standing wisdom?, but also provide new insights. Key outcomes include; i) a demonstration of the need for mass/volume based re-calibration to accurately estimate average ring density; ii) a substantiation of systematic differences in MXD measurements that cautions for great care when combining density datasets for climate reconstructions; and iii) insights into the relevance of analytical measurement resolution in signals derived from tree-ring density data. Finally, we provide recommendations expected to facilitate future inter-comparability and interpretations for global change research.Publisher PDFPeer reviewe

Adults’ number-line estimation strategies: Evidence from eye movements

Although the development of number-line estimation ability is well documented, little is known of the processes underlying successful estimators’ mappings of numerical information onto spatial representations during these tasks. We tracked adults’ eye movements during a number-line estimation task to investigate the processes underlying number-to-space translation, with three main results. First, eye movements were strongly related to the target number’s location, and early processing measures directly predicted later estimation performance. Second, fixations and estimates were influenced by the size of the first number presented, indicating that adults calibrate their estimates online. Third, adults’ number-line estimates demonstrated patterns of error consistent with the predictions of psychophysical models of proportion estimation, and eye movement data predicted the specific error patterns we observed. These results support proportion-based accounts of number-line estimation and suggest that adults’ translation of numerical information into spatial representations is a rapid, online process

Características da oferta de contracepção de emergência na rede básica de saúde do Recife, Nordeste do Brasil

The aim of the study was to describe the use of emergency contraception (EC) in Family Health Units in Recife between March and September, 2011. The questionnaire was answered by 234 professionals, 154 nurses and 80 physicians selected by random sampling in 117 USF. Almost all professionals (90.6%) reported availability of EC in Family Health Unit; physicians and/or nurse were the main prescribers (73.9%); 27.4% knew the distribution strategy by “women’s health kit”. Although 85.0% of professionals have already prescribed the EC, only 8.5% considered the EC as a woman’s right. The majority (80.7%) understand the Family Planning manual of the Ministry of Health and about half (51.2%) understand the Reproductive Rights manual of the municipality’s manual. 51.3% knew the EC action mechanism and 77.4% usually inform women about EC. Among those who do not explain about EC, the main reasons were: “lack of opportunity” (10.0%) for physicians and “to avoid becoming routine” (6.5%) for nurses. Half of the professionals (50.0%) reported prescribing in three recommended situations (unprotected intercourse, rape and failure of contraceptive methodin use) and 65.8% agree that religion interfere in the decision of the prescription/advice. Health professionals have demonstrated sufficient technical knowledge to prescribe EC, but do not recognize it as a right of women. Also, they consider that the influence of religion may interfere with the decision of prescribing and with the use of EC by women.O objetivo do estudo foi descrever as características da utilização da contracepção de emergência (CE) em unidades de saúde da família (USF) da cidade do Recife entre março e setembro de 2011. O questionário foi respondido por 234 profissionais, 154 enfermeiros e 80 médicos selecionados por amostragem aleatória em 117 USF. Quase todos os profissionais (90,6%) informaram disponibilidade da CE na USF; médico e/ou enfermeiro foram os principais dispensadores (73,9%) e 27,4% conheciam a estratégia de distribuição através do “kit saúde da mulher”. Apesar de 85,0% dos profissionais já terem prescrito a CE, apenas 8,5% a consideram como direito da mulher. A maioria (80,7%) conhecia o manual de Planejamento Familiar do Ministério da Saúde e cerca de metade (51,2%) conhecia o manual de Direitos Reprodutivos do município. Entre os entrevistados, 51,3% conheciam o correto mecanismo de ação e 77,4% costumam informar às mulheres sobre CE. Os principais motivos para não informar foram: “falta de oportunidade” (10,0%) para os médicos e “para evitar que se tornem rotina” (6,5%) para os enfermeiros. Metade dos profissionais (50,0%) informaram prescrever nas três situações preconizadas (relação desprotegida, estupro e falha do método contraceptivo em uso) e 65,8% concordam que a religião interfere na decisão da prescrição/orientação. Os profissionais de saúde demonstraram ter conhecimento técnico suficiente para prescrever a CE, porém não a reconhecem como um direito das mulheres. Além disso, consideram que a influência religiosa pode interferir na decisão da prescrição e no uso da CE pelas mulheres

Association of a single nucleotide polymorphism combination pattern of the Klotho gene with non-cardiovascular death in patients with chronic kidney disease

Chronic kidney disease (CKD) is associated with an elevated risk of all-cause mortality, with cardiovascular death being extensively investigated. However, non-cardiovascular mortality represents the biggest percentage, showing an evident increase in recent years. Klotho is a gene highly expressed in the kidney, with a clear influence on lifespan. Low levels of Klotho have been linked to CKD progression and adverse outcomes. Single nucleotide polymorphisms (SNPs) of the Klotho gene have been associated with several diseases, but studies investigating the association of Klotho SNPs with noncardiovascular death in CKD populations are lacking. The main aim of this study was to assess whether 11 Klotho SNPs were associated with non-cardiovascular death in a subpopulation of the National Observatory of Atherosclerosis in Nephrology (NEFRONA) study (n ¼ 2185 CKD patients). After 48 months of follow-up, 62 cardiovascular deaths and 108 non-cardiovascular deaths were recorded. We identified a high non-cardiovascular death risk combination of SNPs corresponding to individuals carrying the most frequent allele (G) at rs562020, the rare allele (C) at rs2283368 and homozygotes for the rare allele (G) at rs2320762 (rs562020 GG/AG þ rs2283368 CC/CT þ rs2320762 GG). Among the patients with the three SNPs genotyped (n ¼ 1016), 75 (7.4%) showed this combination. Furthermore, 95 (9.3%) patients showed a low-risk combination carrying all the opposite genotypes (rs562020 AA þ rs2283368 TT þ rs2320762 GT/TT). All the other combinations [n ¼ 846 (83.3%)] were considered as normal risk. Using competing risk regression analysis, we confirmed that the proposed combinations are independently associated with a higher fhazard ratio [HR] 3.28 [confidence interval (CI) 1.51-7.12]g and lower [HR 6 × 10- (95% CI 3.3 × 10--1.1 × 10-)] risk of suffering a non-cardiovascular death in the CKD population of the NEFRONA cohort compared with patients with the normal-risk combination. Determination of three SNPs of the Klotho gene could help in the prediction of non-cardiovascular death in CKD

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised