bluuebunny/crossref_metadata_2025_split huggingface dataset:
Network Analysis Reveals Different Cellulose Degradation Strategies acrossTrichoderma harzianumStrains Associated with XYR1 and CRE1
Authors: Rosolen Rafaela Rossi , Aono Alexandre Hild , Almeida Déborah Aires , Filho Jaire Alves Ferreira , Horta Maria Augusta Crivelente , de Souza Anete Pereira 
Published: May 2020

AbstractTrichoderma harzianum, whose gene expression is tightly controlled by the transcription factors (TFs) XYR1 and CRE1, is a potential candidate for hydrolytic enzyme production. Here, we performed a network analysis ofT. harzianumIOC-3844 andT. harzianumCBMAI-0179 to explore how the regulation of these TFs varies between these strains. In addition, we explored the evolutionary relationships of XYR1 and CRE1 protein sequences amongTrichodermaspp. The results of theT. harzianumstrains were compared with those ofTrichoderma atrovirideCBMAI-0020, a mycoparasitic species. Although transcripts encoding carbohydrate-active enzymes (CAZymes), TFs, transporters, and proteins with unknown functions were coexpressed withcre1orxyr1, other proteins indirectly related to cellulose degradation were identified. The enriched GO terms describing the transcripts of these groups differed across all strains, and several metabolic pathways with high similarity between both regulators but strain-specific differences were identified. In addition, the CRE1 and XYR1 subnetworks presented different topology profiles in each strain, likely indicating differences in the influences of these regulators according to the fungi. The hubs of thecre1andxyr1groups included transcripts not yet characterized or described as being related to cellulose degradation. The first-neighbor analyses confirmed the results of the profile of the coexpressed transcripts incre1andxyr1. The analyses of the shortest paths revealed that CAZymes upregulated under cellulose degradation conditions are most closely related to both regulators, and new targets between such signaling pathways were discovered. Although the evaluatedT. harzianumstrains are phylogenetically close and their amino acid sequences related to XYR1 and CRE1 are very similar, the set of transcripts related toxyr1andcre1differed, suggesting that eachT. harzianumstrain used a specific regulation strategy for cellulose degradation. More interestingly, our findings may suggest that XYR1 and CRE1 indirectly regulate genes encoding proteins related to cellulose degradation in the evaluatedT. harzianumstrains. An improved understanding of the basic biology of fungi during the cellulose degradation process can contribute to the use of their enzymes in several biotechnological applications and pave the way for further studies on the differences across strains of the same species.
Modeling the photosynthetic system I as complex interacting network
Authors: Montepietra D. , Bellingeri M. , Scotognella F. , Cassi D. 
Published: May 2020

AbstractIn this paper we model the excitation energy transfer (EET) of the photosynthetic system I (PSI) of the common pea plantPisum Sativumas complex interacting network. The magnitude of the link energy transfer between nodes-chromophores is computed by Forster Resonant Energy Transfer (FRET) using the pairwise physical distances between chromophores from the PDB (Protein Data Bank). We measure the global PSI network EET efficiency adopting well-known network theory indicators: the network efficiency (Eff) and the largest connected component (LCC). We find that when progressively removing the weak links of lower EET, the network efficiency (Eff) decreases while the EET paths integrity (LCC) is still preserved. This finding would show that the PSI is a resilient system owning a large window of functioning feasibility and it is completely impaired only when removing most of the network links. Furthermore, we perform nodes removal simulations to understand how the nodes-chromophores malfunctioning may affect the PSI functioning. We discover that the removal of the core chlorophylls triggers the fastest decrease in the network efficiency (Eff), unveiling them as the key component boosting the high EET efficiency. Our outcomes open new perspectives of research, such comparing the PSI energy transfer efficiency of different natural and agricultural plant species and investigating the light-harvesting mechanisms of artificial photosynthesis both in plant agriculture and in the field of solar energy applications.
Following embryonic stem cells, their differentiated progeny, and cell-state changes during iPS reprogramming by Raman spectroscopy
Authors: Germond Arno , Panina Yulia , Shiga Mikio , Niioka Hirohiko , Watanabe Tomonobu M. 
Published: May 2020

AbstractTo monitor cell state transition in pluripotent cells is invaluable for application and basic research. In this study, we demonstrate the pertinence of use non-invasive, label-free Raman spectroscopy to monitor and characterize the cell state transition of mouse stem cells undergoing reprogramming. Using an isogenic cell line of mouse stem cells, reprogramming from neuronal cells was performed, and we showcase a comparative analysis of single cell spectral data of the original stem cells, their neuronal progenitors, and reprogrammed cells. Neural network, regression models, and ratiometric analysis were used to discriminate the cell states and extract several important biomarkers specific to differentiation or reprogramming. Our results indicated that the Raman spectrum allowed to build a low dimensional space allowing to monitor and characterize the dynamics of cell state transition at a single cell level, scattered in heterogeneous populations. Ability of monitoring pluripotency by Raman spectroscopy, and distinguish differences between ES and reprogrammed cells is also discussed.
Closed-loop sacral neuromodulation for bladder function using dorsal root ganglia sensory feedback in an anesthetized feline model
Authors: Ouyang Zhonghua , Barrera Nikolas , Sperry Zachariah J. , Bottorff Elizabeth C. , Bittner Katie C. , Zirpel Lance , Bruns Tim M. 
Published: May 2020

AbstractOveractive bladder patients suffer from a frequent, uncontrollable urge to urinate, which can lead to a poor quality of life. We aim to improve open-loop sacral neuromodulation therapy by developing a conditional stimulation paradigm using neural recordings from dorsal root ganglia (DRG) as sensory feedback. Experiments were performed in 5 anesthetized felines. We implemented a Kalman filter-based algorithm to estimate the bladder pressure in real-time using sacral-level DRG neural recordings and initiated sacral root electrical stimulation when the algorithm detected an increase in bladder pressure. Closed-loop neuromodulation was performed during continuous cystometry and compared to bladder fills with continuous and no stimulation. Overall, closed-loop stimulation increased bladder capacity by 13.8% over no stimulation (p < 0.001) and reduced stimulation time versus continuous stimulation by 57.7%. High-confidence bladder single units had a reduced sensitivity during stimulation, with lower linear trendline fits and higher pressure thresholds for firing observed during stimulation trials. This study demonstrates the utility of decoding bladder pressure from neural activity for closed-loop control of sacral neuromodulation. An underlying mechanism for sacral neuromodulation may be a reduction in bladder sensory neuron activity during stimulation. Real-time validation during behavioral studies is necessary prior to clinical translation of closed-loop sacral neuromodulation.
One gene, multiple ecological strategies: a biofilm regulator is a capacitor for sustainable diversity
Authors: Mhatre Eisha , Snyder Daniel J. , Sileo Emily , Turner Caroline B. , Buskirk Sean W. , Fernandez Nico L. , Neiditch Matthew B. , Waters Christopher M. , Cooper Vaughn S. 
Published: May 2020

AbstractMany bacteria cycle between sessile and motile forms in which they must sense and respond to internal and external signals to coordinate appropriate physiology. Maintaining fitness requires genetic networks that have been honed in variable environments to integrate these signals. The identity of the major regulators and how their control mechanisms evolved remain largely unknown in most organisms. During four different evolution experiments with the opportunist betaproteobacteriumBurkholderia cenocepaciain a biofilm model, mutations were most frequently selected in the conserved generpfR. RpfR uniquely integrates two major signaling systems -- quorum sensing and the motile-sessile switch mediated by cyclic-d-GMP -- by two domains that sense, respond to, and control synthesis of the autoinducer cis-2-dodecenoic acid (BDSF). The BDSF response in turn regulates activity of diguanylate cyclase and phosphodiesterase domains acting on cyclic-di-GMP. Parallel adaptive substitutions evolved in each of these domains to produce unique life history strategies by regulating cyclic-di-GMP levels, global transcriptional responses, biofilm production, and polysaccharide composition. These phenotypes translated into distinct ecology and biofilm structures that enabled mutants to coexist and produce more biomass than expected from their constituents grown alone. This study shows that when bacterial populations are selected in environments challenging the limits of their plasticity, the evolved mutations not only alter genes at the nexus of signaling networks but also reveal the scope of their regulatory functions.Significance statementMany organisms including bacteria live in fluctuating environments requiring attachment and dispersal. These lifestyle decisions require multiple external signals to be processed by several genetic pathways, but how they are integrated is largely unknown. We conducted multiple evolution experiments totaling >20,000 generations withBurkholderia cenocepaciapopulations grown in a model of the biofilm life cycle and identified parallel mutations in one gene,rpfR, that is a conserved central regulator. Because RpfR has multiple sensor and catalytic domains, different mutations can produce different ecological strategies that can coexist and even increase net growth. This study demonstrates that a single gene may coordinate complex life histories in biofilm-dwelling bacteria and that selection in defined environments can reshape niche breadth by single mutations.
Wnt-inducible Lrp6-APEX2 Interacting Proteins Identify ESCRT Machinery and Trk-Fused Gene as Components of the Wnt Signaling Pathway
Authors: Colozza Gabriele , Jami-Alahmadi Yasaman , Dsouza Alyssa , Tejeda-Muñoz Nydia , Albrecht Lauren V. , Sosa Eric , Wohlschlegel James A. , De Robertis Edward M. 
Published: May 2020

AbstractThe canonical Wnt signaling pathway serves as a hub connecting diverse cellular physiological processes, such as β-catenin signaling, differentiation, growth, protein stability, macropinocytosis, and nutrient acquisition in lysosomes. We have proposed that sequestration of β-catenin destruction complex components in multivesicular bodies (MVBs) is required for sustained canonical Wnt signaling. In this study, we investigated the events that follow activation of the canonical Wnt receptor Lrp6 using an APEX2-mediated proximity labeling approach. The Wnt co-receptor Lrp6 was fused to APEX2 and used to biotinylate targets that are recruited near the receptor during Wnt signaling at different time periods. Lrp6 proximity targets were identified by mass spectrometry, and revealed that many components of the ESCRT (Endocytic Sorting Components Required for Transport) machinery interacted with Lrp6 within 5 minutes of Wnt3a treatment. This supports the proposal of a central role of multivesicular endosomes in canonical Wnt signaling. Interestingly, proteomic analyses identified the Trk-fused gene (TFG), previously known to regulate the cell secretory pathway and to be rearranged in thyroid and lung cancers, as being strongly enriched in the proximity of Lrp6. We provide evidence that TFG specifically co-localized with MVBs after Wnt stimulation. TFG depletion with siRNA, or knock-out with CRISPR/Cas9, significantly reduced Wnt/β-catenin signaling in cell culture.In vivo, studies in theXenopussystem showed that TFG is required for endogenous Wnt-dependent embryonic patterning. The results suggest that the multivesicular endosomal machinery and the novel player TFG have important roles in Wnt signaling.SignificanceWnt/β-catenin signaling is a conserved pathway involved in cell differentiation and in the regulation of many other processes, including cell growth and proliferation, macropinocytosis, and cell metabolism. Endocytosis is required to regulate Wnt signaling, but the precise factors at play are still elusive. Here, we describe a biotin-dependent proximity labeling approach using ascorbate peroxidase-tagged Lrp6, a Wnt co-receptor. Proteomic analysis of biotinylated-enriched targets identified numerous multivesicular endosome proteins that were recruited to the receptor shortly after addition of Wnt protein. Additionally, we identified the protein TFG as one of the strongest interactors with Lrp6. TFG co-localized with Wnt-induced multivesicular endosomes.Xenopusembryo assays revealed that TFG is requiredin vivofor canonical Wnt signaling.
Human Life, Rationality and Education
Authors: Kern Andrea 
Published: May 2020

Abstract
In this paper I explore the prospects of a Neo-Aristotelian position—according to which the difference between the human species and non-human animals is a difference in ‘form’—in the context of the question of how the human form of life is related to the idea of education. Two interpretations of this idea have been suggested by contemporary Neo-Aristotelian philosophy that offer contrasting accounts of the role played by education. According to the first, the idea of a formal difference goes with a notion of potentiality, according to which the distinctiveness of the human is mainly a product of education, and hence a matter of second nature. According to the second, the idea of the human is the idea of a formally distinctive kind of first nature that explains the very possibility of education. I maintain that both interpretations do justice to an important aspect of human life yet fail fully to grasp the significance of the notion of ‘form’ that they employ. I argue that to embrace the insight that the difference of the human is a difference in ‘form’, we must think of the human as a form of life whose very concept contains the concept of education. The concept of education, I argue, is a logical concept, contained in the concept of life that it describes.
Cognitive Goods, Open Futures and the Epistemology of Education
Authors: Carter J Adam 
Published: May 2020

Abstract
What cognitive goods do children plausibly have a right to in an education? In attempting to answer this question, I begin with a puzzle centred around Joel Feinberg's observation that a denial of certain cognitive goods can violate a child's right to an open future. I show that propositionalist, dispositionalist and objectualist characterisations of the kinds of cognitive goods children have a right to, run in to problems. A promising alternative is then proposed and defended, one that is inspired in the main by Wittgenstein's ‘hinge’ epistemology as developed in his posthumous On Certainty.
Educating for Intellectual Humility and Conviction
Authors: Pritchard Duncan 
Published: May 2020

Abstract
It is argued that two plausible goals of the educational enterprise are (i) to develop the intellectual character, and thus the intellectual virtues, of the student, and (ii) to develop the student's intellectual self-confidence, such that they are able to have conviction in what they believe. On the face of it, however, these two educational goals seem to be in tension with one another, at least insofar as intellectual humility is a genuine intellectual virtue. This is because intellectual humility seems to require that one does not have conviction in one's beliefs. It is argued that this tension can be avoided so long as we have the right account of intellectual humility in play. This enables us to understand what educating for intellectual humility might involve, and how it might co-exist with the educational development of a student's intellectual self-confidence.
The risk of adverse maternal outcomes in cases of placenta praevia in an Australian population between 2007 and 2017
Authors: Balachandar Kapilesh , Melov Sarah J. , Nayyar Roshini 
Published: May 2020

BackgroundPlacenta praevia is characterised by an inferior placental margin that overlies or falls within 20 mm of the endocervical os. It remains a common cause of antepartum haemorrhage and is associated with adverse maternal and neonatal outcomes.AimsWe aimed to determine the association between antepartum and postpartum haemorrhage and adverse outcomes in cases of placenta praevia.Materials and MethodsThe study population included women diagnosed with placenta praevia, who delivered between 1 April 2007 and 30 April 2017. The endpoints of interest included blood transfusion, emergency caesarean section, peripartum hysterectomy and admission to intensive care.ResultsThere were 513 cases of placenta praevia, of which 67.3% delivered at term. Antepartum haemorrhage was associated with an increased risk of blood transfusion (relative risk (RR) 3.29; 95% CI 2.04–5.32), emergency caesarean section (RR 1.38; 95% CI 1.18–1.62) and preterm delivery, after 32 weeks gestation (RR 4.21; 95% CI 2.77–6.38). Postpartum haemorrhage more than doubled the risk of blood transfusion (RR 9.08 95% CI 5–16.44) and admission to the intensive care unit (RR 10.44; 95% CI 2.34–46.59), as well as increased the risk of peripartum hysterectomy (1.4%). We also described the management of 12 cases of placenta praevia (2.3% of the study population) delivered vaginally.ConclusionsAntepartum and postpartum haemorrhage in cases of placenta praevia are predictors of several adverse outcomes. However, the high rate of term deliveries reaffirms the current practice of expectant management.
Benefits and risks of barefoot harness racing in Standardbred trotters
Authors: Solé Marina , Lindgren Gabriella , Bongcam‐Rudloff Erik , Jansson Anna 
Published: May 2020

AbstractThere is a lack of research on the benefits and risks of shoeing conditions in harness racing. Thus, our objectives were to: (a) investigate whether velocity times (VT; s/km) are affected by racing unshod (N = 76,932 records on 5,247 horses); (b) determine the potential risks of galloping, being penalized, and disqualification when competing unshod (N = 111,755 records on 6,423 horses); and (c) identify additional environmental factors that affect VT and risks. VT was found to be significantly influenced by shoeing condition (e.g., unshod, shod front, shod hind, or fully shod), but also by sex, age, season, track, track condition, start method, start position, distance, and driver‐horse performance level (p < 2e‐16). The risks of galloping and disqualification were significantly influenced by shoeing condition, sex, age, season, track, start method, start position, or driver‐horse performance level (p ≤ .05). Horses racing unshod had 0.7 s/km lower VT than fully shod horses and showed better performance when racing on neutral tracks during the late summer than horses with other shoeing conditions during the same period. However, racing unshod increased the relative risks of galloping and disqualification by 15%–35% in all seasons. Horses shod only on the hind hooves showed better performance than fully shod horses, without higher risks associated with competing unshod.
Dutch trends in the use of potentially harmful medication during pregnancy
Authors: Houben Eline , te Winkel Bernke , Steegers Eric A. P. , Herings Ron M. C. 
Published: May 2020

AimsRecent population‐based data on drug utilization around pregnancy are lacking. This study aims to examine the prevalence of drug exposure in the Netherlands during the preconception, pregnancy and postpartum periods, with special emphasis on trends of potentially harmful medication over the years.MethodsA population‐based study was conducted using records from the PHARMO Perinatal Research Network. From 1999 to 2017, the proportion of pregnancies during which women used any medication or potentially harmful medication was assessed, overall and stratified by timing of exposure relative to pregnancy and by the year of delivery.ResultsOverall, 357 226 (73%) and 166 484 (34%) of 487 122 selected pregnancies were exposed to any and potentially harmful medication, respectively. Among these 487 122 pregnancies, preconception prevalence for use of potentially harmful medication was 43%, 24% during the first trimester, 19% during the second, 16% during the third, and 45% postpartum. A declining trend was observed for exposure to any medication, from 84% in 1999 to 68% in 2017. No clear changes were observed over time for the proportion of pregnancies exposed to potentially harmful medication.ConclusionsOur study shows that the use of potentially harmful medication was high over the last two decades. Although there was a declining trend over the years in overall medication use, during a steady one‐third of pregnancies, women used potentially harmful medication. Our findings highlight the need for an increased sense of urgency among both healthcare providers and women of reproductive age regarding potential risks associated with pharmacological treatment during pregnancy.
Potentially inappropriate medication use and related hospital admissions in aged care residents: The impact of dementia
Authors: Eshetie Tesfahun C. , Roberts Greg , Nguyen Tuan A. , Gillam Marianne H. , Maher Dorsa , Kalisch Ellett Lisa M. 
Published: May 2020

AimsTo determine the prevalence of potentially inappropriate medication (PIM) use at hospital admission and discharge, and the contribution to hospital admission among residential aged care facility residents with and without dementia.MethodsWe conducted a secondary analysis using data from a multihospital prospective cohort study involving consecutively admitted older adults, aged 75 years or older, who were taking 5 or more medications prior to hospital admission and discharged to a residential aged care facility in South Australia. PIM use was identified using the 2015 Screening Tool for Older Persons' Prescription and 2019 Beers criteria. An expert panel of clinicians with geriatric medicine expertise evaluated the contribution of PIM to hospital admission.ResultsIn total, 181 participants were included, the median age was 87.5 years and 54.7% were female. Ninety‐one (50.3%) had a diagnosis of dementia. Participants with dementia had fewer PIMs, according to at least 1 of the 2 screening criteria, than those without dementia, at admission (dementia: 76 [83.5%] vs no dementia: 84 [93.3%], P = .04) and discharge (78 [85.7%] vs 83 [92.2%], P = .16). PIM use was causal or contributory to the admission in 28.1% of study participants (n = 45) who were taking at least 1 PIM at admission.ConclusionsOver 80% of acutely admitted older adults took PIMs at hospital admission and discharge and for over a quarter of these people the admissions were attributable to PIM use. Hospitalisation presents an opportunity for comprehensive medication reviews, and targeted interventions that enhance such a process could reduce PIM use and related harm.