bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reductive TCA cycle enzymes and reductive amino acid synthesis pathways contribute to electron balance in aRhodospirillum rubrumCalvin cycle mutant
Authors: McCully Alexandra L. , Onyeziri Maureen C. , LaSarre Breah , Gliessman Jennifer R. , McKinlay James B. 
Published: April 2019

AbstractPurple nonsulfur bacteria (PNSB) use light for energy and organic substrates for carbon and electrons when growing photoheterotrophically. This lifestyle generates more reduced electron carriers than are required for biosynthesis, even during consumption of some of the most oxidized organic substrates like malate and fumarate. Excess reduced electron carriers must be oxidized for photoheterotrophic growth to occur. Diverse PNSB commonly rely on the CO2-fixing Calvin cycle to oxidize excess reduced electron carriers. Some PNSB also produce H2or reduce terminal electron acceptors as alternatives to the Calvin cycle.Rhodospirillum rubrumCalvin cycle mutants defy this trend by growing phototrophically on malate or fumarate without H2production or access to terminal electron acceptors. We used13C-tracer experiments to examine how aRs. rubrumCalvin cycle mutant maintains electron balance under such conditions. We detected the reversal of some TCA cycle enzymes, which carried reductive flux from malate or fumarate to α-ketoglutarate. This pathway and the reductive synthesis of amino acids derived from α-ketoglutarate are likely important for electron balance, as supplementing the growth medium with α-ketoglutarate-derived amino acids preventedRs. rubrumCalvin cycle mutant growth unless a terminal electron acceptor was provided. Flux estimates also suggested that the Calvin cycle mutant preferentially synthesized isoleucine using the reductive threonine-dependent pathway instead of the less-reductive citramalate-dependent pathway. Collectively, our results suggest that alternative biosynthetic pathways can contribute to electron balance within the constraints of a relatively constant biomass composition.
Data-driven models reveal the organization of diverse cognitive functions in the brain
Authors: Nakai Tomoya , Nishimoto Shinji 
Published: April 2019

AbstractOur daily life is realized by the complex orchestrations of diverse brain functions including perception, decision, and action. One of the central issues in cognitive neuroscience is to reveal the complete representations underlying such diverse functions. Recent studies have revealed representations of natural perceptual experiences using encoding models1–5. However, there has been little attempt to build a quantitative model describing the cortical organization of multiple active, cognitive processes. Here, we measured brain activity using functional MRI while subjects performed over 100 cognitive tasks, and examined cortical representations with two voxel-wise encoding models6. A sparse task-type encoding model revealed a hierarchical organization of cognitive tasks, their representation in cognitive space, and their mapping onto the cortex. A cognitive factor encoding model utilizing continuous intermediate features by using metadata-based inferences7 predicted brain activation patterns for more than 80 % of the cerebral cortex and decoded more than 95 % of tasks, even under novel task conditions. This study demonstrates the usability of quantitative models of natural cognitive processes and provides a framework for the comprehensive cortical organization of human cognition.
Engineering acetyl-CoA metabolic shortcut for eco-friendly production of polyketides triacetic acid lactone inYarrowia lipolytica
Authors: Liu Huan , Marsafari Monireh , Wang Fang , Deng Li , Xu Peng 
Published: April 2019

AbstractAcetyl-CoA is the central metabolic node connecting glycolysis, Krebs cycle and fatty acids synthase. Plant-derived polyketides, are assembled from acetyl-CoA and malonyl-CoA, represent a large family of biological compounds with diversified bioactivity. Harnessing microbial bioconversion is considered as a feasible approach to large-scale production of polyketides from renewable feedstocks. Most of the current polyketide production platform relied on the lengthy glycolytic steps to provide acetyl-CoA, which inherently suffers from complex regulation with metabolically-costly cofactor/ATP requirements. Using the simplest polyketide triacetic acid lactone (TAL) as a target molecule, we demonstrate that acetate uptake pathway in oleaginous yeast (Yarrowia lipolytica) could function as an acetyl-CoA shortcut to achieve metabolic optimality in producing polyketides. We identified the metabolic bottlenecks to rewire acetate utilization for efficient TAL production inY. lipolytica, including generation of the driving force for acetyl-CoA, malonyl-CoA and NADPH. The engineered strain, with the overexpression of endogenous acetyl-CoA carboxylase (ACC1), malic enzyme (MAE1) and a bacteria-derived cytosolic pyruvate dehydrogenase (PDH), affords robust TAL production with titer up to 4.76 g/L from industrial glacier acetic acid in shake flasks, representing 8.5-times improvement over the parental strain. The acetate-to-TAL conversion ratio (0.149 g/g) reaches 31.9% of the theoretical maximum yield. The carbon flux through this acetyl-CoA metabolic shortcut exceeds the carbon flux afforded by the native acetyl-CoA pathways. Potentially, acetic acid could be manufactured in large-quantity at low-cost from Syngas fermentation or heterogenous catalysis (methanol carbonylation). This alternative carbon sources present a metabolic advantage over glucose to unleash intrinsic pathway limitations and achieve high carbon conversion efficiency and cost-efficiency. This work also highlights that low-cost acetic acid could be sustainably upgraded to high-value polyketides by oleaginous yeast species in an eco-friendly and cost-efficient manner.
In vitro evaluation of factor IX as novel treatment for factor XI deficiency
Authors: Bakhtiari Kamran , Meijers Joost C.M. 
Published: April 2019

ABSTRACTFactor XI deficiency is associated with mild to moderate bleeding upon injury. Treatment of bleeding in patients can be a challenge due to the limited availability of factor XI concentrates that may also have thrombotic side effects, and the volume overload as a result of plasma transfusion. In our in vitro study, we established that recombinant factor IX concentrate Benefix® (Pfizer) was able to potently enhance thrombin generation in factor XI depleted plasma when coagulation was initiated via the extrinsic pathway. This was due to the contamination of Benefix® with very low amounts of factor IXa that compensated for the lack of factor XI in plasma. Our data suggest that bleeding due to factor XI deficiency or antithrombotic therapy targeting factor XI may be treated with certain factor IX concentrates, which should be investigated in future clinical studies.
Organization of Associating or Crosslinked Actin Filaments in Confinement
Authors: Koudehi Maral Adeli , Rutkowski David M. , Vavylonis Dimitrios 
Published: April 2019

AbstractA key factor of actin cytoskeleton organization in cells is the interplay between the dynamical properties of actin filaments and cell geometry, which restricts, confines and directs their orientation. Crosslinking interactions among actin filaments, together with geometrical cues and regulatory proteins can give rise to contractile rings in dividing cells and actin rings in neurons. Motivated by recent in vitro experiments, in this work we performed computer simulations to study basic aspects of the interplay between confinement and attractive interactions between actin filaments. We used a spring-bead model and Brownian dynamics to simulate semiflexible actin filaments that polymerize in a confining sphere with a rate proportional to the monomer concentration. We model crosslinking, or attraction through the depletion interaction, implicitly as an attractive short-range potential between filament beads. In confining geometries smaller than the persistence length of actin filaments, we show rings can form by curving of filaments of length comparable to, or longer than the confinement diameter. Rings form for optimal ranges of attractive interactions that exist in between open bundles, irregular loops, aggregated and unbundled morphologies. The probability of ring formation is promoted by attraction to the confining sphere boundary and decreases for large radii and initial monomer concentrations, in agreement with prior experimental data. The model reproduces ring formation along the flat axis of oblate ellipsoids.
Warming increases the cost of growth in a model vertebrate
Authors: Barneche Diego R. , Jahn Miki , Seebacher Frank 
Published: April 2019

Abstract

Growth rates directly influence individual fitness and constrain the flow of energy within food webs. Determining what factors alter the energetic cost of growth is therefore fundamental to ecological and evolutionary models.

Here, we used theory to derive predictions about how the cost of growth varies over ontogeny and with temperature. We tested these predictions by measuring resting oxygen consumption and growth rates of zebrafish (Danio rerio) at four temperature treatments (20°C, 26°C, 29°C, 32°C). We calibrated oxygen consumption for ATP production by measuring the efficiency of mitochondria (P/O ratios) at the end of the experiment.

We show that, when compared to growth rates, rates of resting oxygen consumption exhibited a significantly higher temperature dependence and significantly lower mass scaling. P/O ratios varied substantially among individuals, but did not account for the observed difference in temperature dependence between rates. Consequently, the cost of growth was significantly higher at earlier ontogenetic stages, and it increased twofold between 20°C and 32°C. Temperature systematically decreased the size of adults between 26°C and 32°C.

To the best of our knowledge, our study represents the first attempt to characterise how the cost of growth varies over ontogeny and across temperatures in a model vertebrate. Rising temperatures will substantially alter the structure of ecosystems and the distribution of biomass in food webs because they drive a decline in the average size of individuals, and because higher costs of growth lead to inefficient energy transfer between trophic levels.

A plain language summary is available for this article.
Grassland biodiversity restoration increases resistance of carbon fluxes to drought
Authors: Cole Andrew J. , Griffiths Robert I. , Ward Susan E. , Whitaker Jeanette , Ostle Nicholas J. , Bardgett Richard D. 
Published: April 2019

Abstract

Evidence suggests that the restoration of plant diversity in grasslands not only brings benefits for biodiversity conservation, but also the delivery of ecosystem services. While biodiversity‐function experiments show that greater plant diversity increases resistance of plant productivity to climate extremes, it is not known whether real‐world management options for grassland restoration likewise stabilize ecosystem responses to extreme climate events.

We used a long‐term (23 year) field experiment in northern England to test the hypothesis that management aimed at biodiversity restoration increases the resistance and recovery of ecosystem carbon (C) fluxes to short‐term summer drought. This was tested by measuring plant, soil and microbial responses to a simulated drought in experimental grassland plots where fertilizer application and seed addition have been managed to enhance plant species diversity.

The cessation of fertilizer application brought about small increases in plant species richness. Additionally, cessation of fertilizer application reduced overall plant productivity and promoted hemi‐parasitic plants at the expense of grasses and forbs.

Resistance of CO2 fluxes to drought, measured as ecosystem respiration, was greater in non‐fertilized plots, as lower plant biomass reduced water demand, likely aided by proportionally more hemi‐parasitic plants further reducing plant biomass. Additionally, legumes increased under drought, thereby contributing to overall resistance of plant productivity.

Recovery of soil microbial C and nitrogen was more rapid after rewetting than soil microbial community composition, irrespective of restoration treatment, suggesting high resilience of soil microbial communities to drought.

Synthesis and applications. This study shows that while grassland diversity restoration management increases the resistance of carbon fluxes to drought, it also reduces agricultural yields, revealing a trade‐off for land managers. Furthermore legumes, promoted through long‐term restoration treatments, can help to maintain plant community productivity under drought by increasing their biomass. As such, grassland management strategies not only have consequences for ecosystem processes, but also the capacity to withstand extreme weather events.
Phenology of farmland floral resources reveals seasonal gaps in nectar availability for bumblebees
Authors: Timberlake Thomas P. , Vaughan Ian P. , Memmott Jane 
Published: April 2019

Abstract

Floral resources are known to be important in regulating wild pollinator populations and are therefore an important component of agri‐environment and restoration schemes which aim to support pollinators and their associated services. However, the phenology of floral resources is often overlooked in these schemes — a factor which may be limiting their success.

Our study characterizes and quantifies the phenology of nectar resources at the whole‐farm scale on replicate farms in Southwestern UK throughout the flowering season. We quantify the corresponding nectar demands of a subset of common wild pollinators (bumblebees) to compare nectar supply and pollinator demand throughout the year, thereby identifying periods of supply‐demand deficit.

We record strong seasonal fluctuations in farmland nectar supplies, with two main peaks of nectar production (May and July) and a considerable “June Gap” in between. March and August/September are also periods of low nectar availability.

Comparing the phenology of nectar supply with the phenology of bumblebee nectar demand reveals “hunger gaps” during March and much of August/September when supply is unlikely to meet demand.

Permanent pasture and woodland produced the greatest share of farmland nectar because of their large area; however, linear features such as hedgerows and field margins provided the greatest nectar per unit area. Fifty percent of total nectar was supplied by just three species (Allium ursinum, Cirsium arvense and Trifolium repens), but some less productive species (e.g. Hedera helix and Taraxacum agg.) were important in ensuring phenological continuity of nectar supply.

Synthesis and applications. By comparing the phenology of farmland nectar supply with the phenology of pollinator demand, we demonstrate that the timing of nectar supply may be as important as total nectar production in limiting farmland pollinator populations. Considering phenology in the design of agri‐environment or restoration schemes is therefore likely to improve their suitability for pollinators. Plant species which flower during periods of resource deficit (early spring and late summer) should be prioritized in schemes which aim to conserve or restore pollinator populations. Maintaining a range of semi‐natural habitats with complementary flowering phenologies (e.g. woodland, hedgerows and field margins) will ensure a more continuous supply of nectar on farmland, thereby supporting pollinators for their entire flight season.
Shock index thresholds to predict adverse outcomes in maternal hemorrhage and sepsis: A prospective cohort study
Authors: Nathan Hannah L. , Seed Paul T. , Hezelgrave Natasha L. , De Greeff Annemarie , Lawley Elodie , Anthony John , Steyn Wilhelm , Hall David R. , Chappell Lucy C. , Shennan Andrew H. 
Published: April 2019

AbstractIntroductionShock index (SI) is a predictor of hemodynamic compromise in obstetric patients. The SI threshold for action is not well understood. We aimed to evaluate SI thresholds as predictors of outcomes in obstetric patients.Material and methodsWe undertook a prospective cohort study at three South African hospitals of women with postpartum hemorrhage (n = 283) or maternal sepsis (n = 126). The “first” and “worst” SI following diagnosis were recorded. SI was compared with conventional vital signs as predictors of outcomes. The performance of SI <.9, SI .9‐1.69 and SI ≥1.7 to predict outcomes (maternal death; Critical Care Unit admission; major procedure; hysterectomy) and hemorrhage‐specific outcomes (lowest hemoglobin <70 g/l; blood transfusion ≥4 IU) were evaluated.Results“First” SI was one of two best performing vital signs for every outcome in postpartum hemorrhage and sepsis. In hemorrhage, risk of all outcomes increased with increasing “first” SI; for blood transfusion ≥4 IU odds ratio was 4.24 (95% confidence interval 1.25‐14.36) for SI ≥1.7 vs SI .9‐1.69. In sepsis, risk of all outcomes increased with increasing “worst” SI. Sensitivity, specificity, positive and negative predictive values of “first” SI <.9 vs SI ≥.9 for maternal death were 100.0%, 55.2%, 4.6% and 100.0%, respectively, in hemorrhage and 80.0%, 50.4%, 12.3% and 96.7%, respectively, in sepsis.ConclusionsThe shock index was a consistent predictor of outcomes compared with conventional vital signs in postpartum hemorrhage and sepsis. SI <.9 performed well as a rule‐out test and SI .9‐1.69 and SI ≥1.7 indicated increased risk of all outcomes in both cohorts. These thresholds may alert to the need for urgent intervention and prevent maternal deaths.
Evaluation of in vitro hemolysis and platelet activation of a newly developed maglev LVAD and two clinically used LVADs with human blood
Authors: Berk Zachary B. K. , Zhang Jiafeng , Chen Zengsheng , Tran Douglas , Griffith Bartley P. , Wu Zhongjun J. 
Published: April 2019

AbstractIn vitro hemolysis testing remains one of the most important performance measures to judge the hemocompatibility of a left ventricular assist device (LVAD). Clinically relevant operating conditions and appropriate testing blood are essential to infer in vitro data for potential clinical use. This in vitro study was carried out to evaluate and compare the hemolytic performance of a newly developed magnetically levitated (maglev) LVAD (CH‐VAD) with two clinically used LVADs (HVAD and HeartMate II (HMII)) using fresh human blood. A small volume (~300 mL) in vitro circulating flow loop was constructed with a LVAD generated flow of 4.5 L/min at the nominal or reported clinical operating speed for each LVAD. The blood was circulated in the loop for 4 hours with samples drawn at baseline and hourly. Plasma‐free hemoglobin (PFH) concentrations in the hourly blood samples were determined with spectrophotometry. Normalized index of hemolysis (NIH) was calculated to compare the hemolytic performance of the CH‐VAD and the two reference LVADs. Platelet activation was measured with flow cytometry. The experimental test for each device was repeated at least 7 times. The data from this study showed that all the three LVADs generated very low hemolysis (NIH <0.01 g/100 L). The CH‐VAD was found to have a significantly lower NIH value (0.00135 ± 0.00032 g/100 L) compared to the HVAD (0.00525 ± 0.00183 g/100 L) and the HMII (0.00583 ± 0.00182 g/100 L). No statistically significant difference in device‐generated hemolysis was found between the HVAD and the HMII. The level of platelet activation induced by the CH‐VAD is significantly lower than those by the HVAD and the HMII. The data suggest that the shear‐induced hemolysis and platelet activation of the CH‐VAD are acceptable relative to the two LVADs currently in clinical use.
Cohort study showed that growth rate increment has not been enough to prevent growth retardation of preterm infants and raised concerns about unbalanced growth
Authors: Zozaya Carlos , Avila‐Alvarez Alejandro , Couce María L. , García‐Muñoz Rodrigo Fermín , Arruza Luis , Fernandez‐Perez Cristina , Castro Abdón , Cuesta María Teresa , Vacas Beatriz , Vento Máximo , Saenz de Pipaón Miguel 
Published: April 2019

AbstractAimWe describe the postnatal weight gain, linear and head growth trends of surviving preterm infants from 2005 to 2017.MethodsMulticentre cohort study, including surviving preterm infants <32 weeks (n = 21 084), from the Spanish Neonatal Network database, without major congenital malformations who were less than 50 weeks postmenstrual age at discharge. Outcomes were weight gain (g/kg/day), linear and head growth (cm/week) and changes in weight, length and head circumference z‐scores from birth to discharge. The study period was divided into 2005–8, 2009–11, 2012–14 and 2015–17.ResultsWeight gain, linear growth and head growth were slightly higher in 2015–2017 than in 2005–2008: 12.2 ± 2.6 to 13.1 ± 2.5 g/kg/day, 0.98 ± 0.6 to 1.03 ± 0.6 cm/week and 0.76 ± 0.2 to 0.77 ± 0.3 cm/week, respectively. It was associated with a decreased fall in weigh, length and head circumference z‐scores from birth to discharge (−1.32 ± 0.9 to −1.01 ± 0.84, −1.38 ± 1.2 to −1.18 ± 1.2 and −0.41 ± 1.2 to −0.33 ± 1.3, respectively).ConclusionPostnatal growth restriction remained a common complication of prematurity despite some increment over the last years. Growth disproportionality seemed to be worsening as weight gain was increased more than linear growth.
Systematic review: long‐term cognitive and behavioural outcomes of neonatal hypoxic–ischaemic encephalopathy in children without cerebral palsy
Authors: Schreglmann Magdalena , Ground Amy , Vollmer Brigitte , Johnson Mark J. 
Published: April 2019

AbstractAimTo evaluate long‐term cognitive and behavioural outcomes of children with neonatal hypoxic–ischaemic encephalopathy (HIE) in the absence of cerebral palsy (CP).MethodsA systematic search was performed on five databases (EMBASE, Medline, PubMed, Web of Science, PsycInfo). Randomised controlled trials, non‐randomised controlled trials, or observational studies, published between 1990 and 2017, that reported long‐term (age greater than or equal to four years) cognitive and/or behavioural outcomes of neonatal HIE without CP were included.ResultsSeven articles met the inclusion criteria (n = 352 total participants, n = 53 treated with therapeutic hypothermia). Studies reporting cognitive outcome demonstrate impairment of general cognitive abilities in 25–63% of participants with HIE without CP. Specific cognitive difficulties were reported in two studies for attention, executive functioning, memory function and language. Results regarding behavioural outcome possibly indicate a higher risk of difficulties.ConclusionA substantial proportion of children with neonatal HIE who survive without CP are at increased risk of general and/or specific cognitive impairments. Behavioural problems may be more common, but evidence is limited. Results highlight the importance of comprehensive long‐term follow‐up to identity difficulties and enable intervention to optimise educational achievement and behavioural adjustment.