bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hyperthermal-driven mass extinctions: killing models during the Permian–Triassic mass extinction
Authors: Benton Michael J. 
Published: September 2018

Many mass extinctions of life in the sea and on land have been attributed to geologically rapid heating, and in the case of the Permian–Triassic and others, driven by large igneous province volcanism. The Siberian Traps eruptions raised ambient temperatures to 35–40°C. A key question is how massive eruptions during these events, and others, could have killed life in the sea and on land; proposed killers are reviewed here. In the oceans, benthos and plankton were killed by anoxia–euxinia and lethal heating, respectively, and the habitable depth zone was massively reduced. On land, the combination of extreme heating and drought reduced the habitable land area, and acid rain stripped forests and soils. Physiological experiments show that some animals can adapt to temperature rises of a few degrees, and that some can survive short episodes of increases of 10°C. However, most plants and animals suffer major physiological damage at temperatures of 35–40°C. Studies of the effects of extreme physical conditions on modern organisms, as well as assumptions about rates of environmental change, give direct evidence of likely killing effects deriving from hyperthermals of the past.
This article is part of a discussion meeting issue ‘Hyperthermals: rapid and extreme global warming in our geological past’.
Neural Flip-Flops I: Short-Term Memory
Authors: Yoder Lane 
Published: September 2018

AbstractThe networks proposed here show how neurons can be connected to form flip-flops, the basic building blocks in sequential logic systems. The novel neural flip-flops (NFFs) are explicit, dynamic, and can generate known phenomena of short-term memory.For each network design, all neurons, connections, and types of synapses are shown explicitly. The neurons’ operation depends only on explicitly stated, minimal properties of excitement and inhibition. This operation is dynamic in the sense that the level of neuron activity is the only cellular change, making the NFFs’ operation consistent with the speed of most brain functions. Memory tests have shown that certain neurons fire continuously at a high frequency while information is held in short-term memory. These neurons exhibit seven characteristics associated with memory formation, retention, retrieval, termination, and errors. One of the neurons in each of the NFFs produces all of the characteristics. This neuron and a second neighboring neuron together predict eight unknown phenomena. These predictions can be tested by the same methods that led to the discovery of the first seven phenomena. NFFs, together with a decoder from a previous paper, suggest a resolution to the longstanding controversy of whether short-term memory depends on neurons firing persistently or in brief, coordinated bursts.Two novel NFFs are composed of two and four neurons. Their designs follow directly from a standard electronic flip-flop design by moving each negation symbol from one end of the connection to the other. This does not affect the logic of the network, but it changes the logic of each component to a logic function that can be implemented by a single neuron. This transformation is reversible and is apparently new to engineering as well as neuroscience.
RADI (Reduced Alphabet Direct Information): Improving execution time for direct-coupling analysis
Authors: Anton Bernat , Besalú Mireia , Fornes Oriol , Bonet Jaume , De las Cuevas Gemma , Fernández-Fuentes Narcís , Oliva Baldo 
Published: September 2018

AbstractMotivationDirect-coupling analysis (DCA) for studying the coevolution of residues in proteins has been widely used to predict the three-dimensional structure of a protein from its sequence. Current algorithms for DCA, although efficient, have a high computational cost of determining Direct Information (DI) values for large proteins or domains. In this paper, we present RADI (Reduced Alphabet Direct Information), a variation of the original DCA algorithm that simplifies the computation of DI values by grouping physicochemically equivalent residues.ResultsWe have compared the first top ranking 40 pairs of DI values and their closest paired contact in 3D. The ranking is also compared with results obtained using a similar but faster approach based on Mutual Information (MI). When we simplify the number of symbols used to describe a protein sequence to 9, RADI achieves similar results as the original DCA (i.e. with the classical alphabet of 21 symbols), while reducing the computation time around 30-fold on large proteins (with length around 1000 residues) and with higher accuracy than predictions based on MI. Interestingly, the simplification produced by grouping amino acids into only two groups (polar and non-polar) is still representative of the physicochemical nature that characterizes the protein structure, having a relevant and useful predictive value, while the computation time is reduced between 100 and 2500-fold.AvailabilityRADI is available at https://github.com/structuralbioinformatics/RADIContactbaldo.oliva@upf.eduSupplementary informationSupplementary data is available in the git repository.
Structural Adaptation of Darunavir Analogs Against Primary Resistance Mutations in HIV-1 Protease
Authors: Lockbaum Gordon J. , Leidner Florian , Rusere Linah N. , Henes Mina , Kosovrasti Klajdi , Nalivaika Ellen A. , Ali Akbar , Yilmaz Nese Kurt , Schiffer Celia A. 
Published: September 2018

AbstractHIV-1 protease is one of the prime targets of agents used in antiretroviral therapy against HIV. However, under selective pressure of protease inhibitors, primary mutations at the active site weaken inhibitor binding to confer resistance. Darunavir (DRV) is the most potent HIV-1 protease inhibitor in clinic; resistance is limited, as DRV fits well within the substrate envelope. Nevertheless, resistance is observed due to hydrophobic changes at residues including I50, V82 and I84 that line the S1/S1’ pocket within the active site. Through enzyme inhibition assays and a series of 12 crystal structures, we interrogated susceptibility of DRV and two potent analogs to primary S1’ mutations. The analogs had modifications at the hydrophobic P1’ moiety to better occupy the unexploited space in the S1’ pocket where the primary mutations were located. Considerable losses of potency were observed against protease variants with I84V and I50V mutations for all three inhibitors. The crystal structures revealed an unexpected conformational change in the flap region of I50V protease bound to the analog with the largest P1’ moiety, indicating interdependency between the S1’ subsite and the flap region. Collective analysis of protease-inhibitor van der Waals (vdW) interactions in the crystal structures using principle component analysis indicated I84V mutation underlying the largest variation in the vdW contacts. Interestingly, the principle components were able to distinguish inhibitor identity and relative potency solely based on vdW interactions of active site residues in the crystal structures. Our results reveal the interplay between inhibitor P1’ moiety and primary S1’ mutations, as well as suggesting a novel method for distinguishing the interdependence of resistance through principle component analyses.
Relative Reduction of the Biological and phylogenetic diversity of oral microbiome in diabetic and pre-diabetic subjects
Authors: Saeb Amr T. M. , Al-Rubeaan Khalid A. , Aldosary Khalid , Udaya Raja G. K. , Mani Balavenkatesh , Abouelhoda Mohamed , Tayeb Hamsa T. 
Published: September 2018

AbstractBackgroundThere is a suggested reciprocal relationship between oral health and systemic disease such as type 2 diabetes. In this relationship, a systemic disease predisposing to oral infection, and when that infection is present, the oral infection aggravates the progression of the systemic disease. Several studies suggested that some oral microbiome constituents are linked to both diabetes, metabolic syndrome and obesity. This study aims to compare the microbial diversity and population structure of oral microbiome among normoglycemic, impaired glucose tolerance (IGT) and diabetic subjects.MethodologyThis study followed a case-control design (15 T2D patients, 10 IGTs and, 19 controls). Patient records were screened as per the inclusion and exclusion criteria. Assessment of periodontitis and oral health was performed to all subjects. DNA Isolation purification and quantification from collected Saliva samples were performed. 16SrRNA hypervariable regions were amplified and sequenced. Generated sequences were subjected to bioinformatics analysis. Statistical analysis and diversity indices were computed with the statistical software R, the vegan R-package, and Past318 software.ResultsA total observed number of 551 OTUs. A clear reduction of the number of species (OTUs) was observed in both IGT (412) and diabetic group (372) compared with the normoglycemic group (502). This was associated with a similar pattern of biological diversity among the three groups. Phylogenetic diversity (PD-SBL) value in the normoglycemic group was higher than the diabetic group. The diabetic group had the highest evenness value and the highest microbiome bacterial pathogenic content.ConclusionWe observed a clear reduction in the biological and phylogenetic diversity in the diabetic and pre-diabetic oral microbiome in comparison with the normoglycemic oral microbiome. However, this reduction was associated with an increase in the pathogenic content of the hyperglycemic microbiomes.
Intensive and Specific Feedback Self-control of the Argonautes and MicroRNA Targeting Activity
Authors: Wang Degeng , Gill Audrey , Zhang Fangyuan 
Published: September 2018

AbstractThe miRNA pathway consists of three segments – biogenesis, targeting and downstream regulatory effectors. How the cells control their activities remains incompletely understood. This study explored the intrinsically complex miRNA-mRNA targeting relationships, and suggested differential mechanistic control of the three segments. We first analyzed evolutionarily conserved sites for conserved miRNAs in the human transcriptome. Strikingly, AGO1, AGO2 and AGO3 are all among the top 14 mRNAs with highest numbers of unique conserved miRNA sites, and so is ANKRD52, the phosphatase regulatory subunit of the recently identified AGO phosphorylation cycle (AGOs, CSNK1A1, ANKRD52 and PPP6C). The mRNAs for TNRC6, which acts together with loaded AGO to channel miRNA-mediated regulation actions onto specific mRNAs, are also heavily miRNA-targeted. Moreover, mRNAs of the AGO phosphorylation cycle share much more than expected miRNA binding sites. In contrast, upstream miRNA biogenesis mRNAs do not display these characteristics, and neither do the downstream regulatory effector mRNAs. In a word, miRNAs heavily and directly feedback-regulate their targeting machinery mRNAs, but neither upstream biogenesis nor downstream regulatory effector mRNAs. The observation was then confirmed with experimentally determined miRNA-mRNA target relationships. In summary, our exploration of the miRNA-mRNA target relationship uncovers intensive, and specific, feedback auto-regulation of miRNA targeting activity directly by miRNAs themselves, i.e., segment-specific feedback auto-regulation of miRNA pathway. Our results also suggest that the complexity of miRNA-mRNA targeting relationship – a defining feature of miRNA biology – should be a rich source for further functional exploration.
Relationships of trainee dentists’ empathy and communication characteristics with simulated patients’ assessment in medical interviews
Authors: Watanabe Sho , Yoshida Toshiko , Kono Takayuki , Taketa Hiroaki , Shiotsu Noriko , Shirai Hajime , Torii Yasuhiro 
Published: September 2018

AbstractObjectivesWe aimed to clarify the characteristics of communication between trainee dentists and simulated patients (SPs) and to examine how the level of trainee dentists’ self-reported empathy influences assessment by SPs in medical interviews.Materials and methodsThe study involved 100 trainee dentists at Okayama University Hospital and eight SPs. The trainee dentists conducted initial interviews with the SPs after completing the Japanese version of the Jefferson Scale of Empathy. Their interviews were recorded and analyzed using the Roter Interaction Analysis System. The SPs assessed the trainees’ communication immediately after each interview. The trainee dentists were classified into two groups (more positive and less positive groups) according to SP assessment scores.ResultsCompared with the less positive trainees, the more positive trainees scored higher on the [Emotional expression] and lower on the [Medical data gathering] Roter Interaction Analysis System categories. There was no difference in [Dental data gathering] between the two groups. The SPs of more positive trainees had higher rates of [Positive talk] and [Emotional expression] and lower rates of [Medical information giving] and [Dental information giving]. The trainees with more positive ratings from SPs had significantly higher Jefferson Scale of Empathy total scores.ConclusionThe results of this study suggest that responding to the SPs’ emotions is a relevant characteristic of dentist–SP communication to SPs’ positive assessment in medical interviews. Further, trainees’ self-reported empathy was related with the SPs’ assessment of trainees’ communication, which indicated that patient satisfaction can be improved by increasing the dentist’s empathy. Thus, an empathic attitude among dentists is a significant determinant of patient satisfaction.
Metagenomic profiling of ticks: identification of novel rickettsial genomes and detection of tick borne canine parvovirus
Authors: Ravi Anuradha , Ereqat Suheir , Al-Jawabreh Amer , Abdeen Ziad , Shamma Omar Abu , Hall Holly , Pallen Mark J. , Nasereddin Abedelmajeed 
Published: September 2018

AbstractBackgroundAcross the world, ticks act as vectors of human and animal pathogens. Ticks rely on bacterial endosymbionts, which often share close and complex evolutionary links with tick-borne pathogens. As the prevalence, diversity and virulence potential of tick-borne agents remain poorly understood, there is a pressing need for microbial surveillance of ticks as potential disease vectors.Methodology/Principal FindingsWe developed a two-stage protocol that includes 16S-amplicon screening of pooled samples of hard ticks collected from dogs, sheep and camels in Palestine, followed by shotgun metagenomics on individual ticks to detect and characterise tick-borne pathogens and endosymbionts. Two ticks isolated from sheep yielded an abundance of reads from the genusRickettsia, which were assembled into draft genomes. One of the resulting genomes was highly similar toRickettsia massiliaestrain MTU5. Analysis of signature genes showed that the other represents the first genome sequence of the potential pathogenCandidatusRickettsia barbariae. Ticks from a dog and a sheep yielded draft genome sequences of strains of the Coxiella-like endosymbiontCandidatusCoxeilla mudrowiae. A sheep tick yielded sequences from the sheep pathogenAnaplasma ovis, whileHyalommaticks from camels yielded sequences belonging toFrancisella-like endosymbionts. From the metagenome of a dog tick from Jericho, we generated a genome sequence of a canine parvovirus.SignificanceHere, we have shown how a cost-effective two-stage protocol can be used to detect and characterise tick-borne pathogens and endosymbionts. In recovering genome sequences from an unexpected pathogen (canine parvovirus) and a previously unsequenced pathogen (CandidatusRickettsia barbariae), we demonstrate the open-ended nature of metagenomics. We also provide evidence that ticks can carry canine parvovirus, raising the possibility that ticks might contribute to the spread of this troublesome virus.Author SummaryWe have shown how DNA sequencing can be used to detect and characterise potentially pathogenic microorganisms carried by ticks. We surveyed hard ticks collected from domesticated animals across the West Bank territory of Palestine. All the ticks came from species that are also capable of feeding on humans. We detected several important pathogens, including two species ofRickettsia, the sheep pathogenAnaplasma ovisand canine parvovirus. These findings highlight the importance of hard ticks and the hazards they present for human and animal health in Palestine and the opportunities presented by high-throughput sequencing and bioinformatics analyses of DNA sequences in this setting.
Gp78 E3 ubiquitin ligase mediates both basal and damage-induced mitophagy
Authors: Joshi Bharat , Mohammadzadeh Yayha , Gao Guang , Nabi Ivan R. 
Published: September 2018

AbstractMitophagy, the elimination of mitochondria by the autophagy machinery, evolved to monitor mitochondrial health and maintain mitochondrial integrity. PINK1 is a sensor of mitochondrial health that recruits Parkin and other mitophagy-inducing ubiquitin ligases to depolarized mitochondria. However, mechanisms underlying mitophagic control of mitochondrial homeostasis, basal mitophagy, remain poorly understood. The Gp78 E3 ubiquitin ligase, an endoplasmic reticulum membrane protein, induces mitochondrial fission, endoplasmic reticulum-mitochondria contacts and mitophagy of depolarized mitochondria. CRISPR/Cas9 knockout of Gp78 in HT-1080 fibrosarcoma cells results in reduced ER-mitochondria contacts, increased mitochondrial volume and resistance to CCCP-induced mitophagy. Knockdown (KD) of the essential autophagy protein ATG5 increased mitochondrial volume of wild-type cells but did not impact mitochondrial volume of Gp78 knockout cells. This suggests that endogenous Gp78 actively eliminates mitochondria by autophagy in wild-type HT-1080 cells. Damage-induced mitophagy of depolarized mitochondria, in the presence of CCCP, but not basal mitophagy was prevented by knockdown of PINK1. This suggests that endogenous Gp78 plays dual roles in mitophagy induction: 1) control of mitochondrial homeostasis through mitophagy of undamaged mitochondria; and 2) elimination of damaged mitochondria through PINK1.
Ovule bet‐hedging at high elevation in the South American Andes: Evidence from a phylogenetically controlled multispecies study
Authors: Arroyo Mary T. K. , Pérez Fernanda , Jara‐Arancio Paola , Pacheco Diego , Vidal Paula , Flores María Francisca 
Published: September 2018

Abstract

How animal‐pollinated plants support low and stochastic pollination in the high alpine is a key question in plant ecology. The ovule bet‐hedging hypothesis proposes compensation for stochastic pollination via ovule oversupply in flowers allowing the benefits of windfall pollination events to be reaped. Under this hypothesis, ovule number is expected to increase from tree line upward on high mountains characterized by steep declines in flower visitation rates and increasingly more variable pollination.

Ovule/floret number was investigated for a total of 174 simple‐flowered and pseudanthial species in the central Chilean Andes (2,100–3,650 m.a.s.l.). Phylogenetic reconstruction was undertaken using ITS sequences and a constrained ordinal‐level backbone reflecting the APG‐IV topology. Ovule/floret number was modelled with ordinary least squares regression (OLS) and phylogenetic generalized least squares regression (PGLS) with elevation, floral biomass, life history, pollinator efficiency, pollination generalization, and seasonal flowering period as explanatory variables.

The best performing OLS and PGLS models for simple‐flowered species consistently included vegetation belt and floral biomass, and with PGLS, pollination efficiency and flowering period. For pseudanthial species, explanatory variables were always floral biomass and its interaction with elevation. Effects of life history and generalized pollination was not found. Ovule/floret number showed high phylogenetic signal, increased with floral biomass and was generally higher in the upper alpine belt in both floral categories. Simple‐flowered species with efficient pollination and flowering early, respectively, had larger ovule numbers.

Synthesis. Ovule number increases with elevation in the central Chilean alpine in two separate floral groups independently of some effects of flowering period and pollinator efficiency. Greater disparity in pollen deposition on stigmas than with inefficient pollination under low visitation rates might explain the association between efficient pollination and higher ovule numbers. Our study provides the first empirical evidence for ovule bet‐hedging in the alpine environment. Future studies on the ovule bet‐hedging hypothesis should include a measure of flower size.
Heterotrophic substrate specificity in the aquatic environment: The role of microscale patchiness investigated using modelling
Authors: Hellweger Ferdi L. 
Published: September 2018

SummaryRecent observations of natural bacterial communities show high genetic diversity in organic carbon uptake systems (microdiversity) and specificity in substrate species taken up. This seemingly contradicts a large body of literature from laboratory experiments under nutrient‐limiting conditions, where mixed substrate use is the rule. This apparent discrepancy can be resolved by realizing that bacteria in the natural aquatic environment encounter nutrients as high‐concentration patches. They may live in an ecologically nutrient‐limiting environment, but they are rarely in a biologically nutrient‐limited state. Rather they switch between non‐growing and nutrient‐replete states. During nutrient‐replete growth the metabolism is saturated and assimilating additional substrates does not increase the growth rate, but carrying the assimilation system constitutes a cost. Consequently, the specialist strategy is beneficial, which is consistent with observations from laboratory experiments. When the bacteria are not growing, the added cost also reduces the fitness of the generalist species. A simple mathematical model encompassing the relevant mechanisms is developed and parameterized realistically based on the literature. The model predicts that, under pulsed conditions, specialization is beneficial when the metabolic cost of an additional uptake system is more than ~0.5% of the total metabolic cost, which is a reasonable estimate and illustrates that this is a plausible hypothesis.
A Social‐Ecological Systems Approach to Enhance Sustainable Farming and Forestry in the EU
Authors: Dwyer Janet , Berriet‐Solliec Marielle , Lataste François Gaël , Short Chris , Maréchal Anne , Hart Kaley 
Published: September 2018

SummaryThe two concepts of public goods and ecosystem services are often used to describe the same welfare benefits potentially generated by agriculture and forestry, but they originate from different perspectives and each offer only partial analysis of these relationships. A more holistic approach – Social‐Ecological Systems (SES) – has been adapted and applied in new research to understand more fully how the relationships can best be characterised, and beneficial change promoted, through policy reforms and practical action. An important and novel part of the description of a SES, as developed under the PEGASUS project, is the assessment of its ‘valorisation cascade’. Through the mapping and consideration of assets, actors, interactions, drivers and the nature of the valorisation cascade in 34 diverse case studies, the project highlighted the importance of multi‐actor approaches and social processes to foster beneficial change. These include collective action, co‐learning and trust between actors, promoting experimentation and innovation, developing public and/or consumer awareness and identifying new valorisation options, including via commercial supply chains and enhanced community involvement.