bluuebunny/crossref_metadata_2025 huggingface dataset:
Reproductive biology and maternal care of neonates in southern African python (Python natalensis)
Authors: Alexander G. J.
Published: March 2018

Reproductive strategies such as parental care have been pivotal in evolutionary innovations such as endothermy in birds and mammals. The diversity of reproductive biology across the squamates provides a unique opportunity for elucidating the selective forces responsible for the evolution of various reproductive strategies. Here, I report on the reproductive biology of the southern African python (Python natalensis), based on a 7‐year study of free‐ranging pythons, revealing a behavioural complexity not usually expected for snakes. Mating occurred in the austral winter, with individual males following females for more than 2 months. As is typical for pythons, females brooded eggs by coiling around the clutch. Females are capital breeders; they lost ~40% body mass during a breeding event and did not breed in consecutive years. There was no evidence of the facultative thermogenesis that has been reported in congeners, suggesting that facultative thermogenesis has arisen independently more than once in Python. Reproductive females thermoregulated more carefully than non‐reproductives, maintaining higher, more stable Tbs at all stages of reproduction, especially while brooding. This was achieved by a stereotypic basking regime facilitated by ‘facultative melanism’, with females darkening significantly for the entire breeding event. Mothers remained with neonates at the nest site for approximately 2 weeks after hatching. During this time, mothers alternated between brief bouts of basking on the surface and coiling around the hatched eggs, on which the neonates rested. Neonates formed an aggregation near the burrow entrance to bask during the day, individually returning to the nest intermittently throughout the day. During the night, neonates remained within the mother's coils on the hatched eggs. This study highlights the diversity of reproductive biology within Python and cautions against generalization in this regard. This is the first unambiguous report of maternal care of neonates in an oviparous snake.
Who Are Our People? Toward a Christian Witness against Borders
Authors: Ashworth Justin P.
Published: March 2018

Christian arguments for state borders are grounded in the preferential option for one's people, that is, the conviction that the needs of co‐citizens must be given priority over those of foreigners. Theologians often find support for this conviction in the doctrines of human finitude and divine providence: limited resources make it impossible to love all people equally, so we must choose where to start; since God has providentially placed near‐neighbors (citizens) in our paths, we honor God's design by keeping in mind their proximate needs in our moral deliberations. I argue that there are several flaws in such defenses of borders. First, they overlook the violence inherent in actually‐existing border practices; second, they misidentify fellow citizens as our people, thereby underwriting the church's captivity to state violence. I argue that a sounder theological view of borders requires Christians to adopt a preferential option for God's people. The church catholic is a borderless people committed to bodily solidarity and sharing with the vulnerable. Inasmuch as the church is a people already gathered in anticipation of the final joining of all things in Jesus Christ, ecclesial borderlessness serves as the horizon for all peoples.
Pain after root canal treatment with different instruments: A systematic review and meta‐analysis
Authors: Sun C , Sun J , Tan M , Hu B , Gao X , Song J
Published: March 2018

The aims of this systematic review were to compare the incidence and intensity of postoperative pain after single‐visit root canal treatment using manual, rotary, and reciprocating instruments. An extensive literature search in PubMed,EMBASE, Cochrane Library, and Web of Science was performed to identify investigations that evaluated the effects of different instruments on postendodontic pain. Meta‐analyses and additional analyses, including subgroup and sensitivity analyses, were conducted. We included seventeen trials in this study. Pooled results showed that patients treated with rotary instruments experienced a significantly lower incidence of postoperative pain (RR, 0.32,p = .0005) and reduced pain intensity than did patients treated with manual instruments. In addition, patients treated with multiple rotary‐file systems experienced a significantly lower incidence of postoperative pain than did those treated with reciprocating systems (RR, 0.73;p < .0001). The use of rotary instruments contributed to a lower incidence and intensity of postoperative pain than did the use of hand files in patients who received single‐visit root canal treatment. In addition, the use of multiple rotary‐file systems contributed to a lower incidence of postoperative pain than did the use of reciprocating systems.
Spatially explicit patterns in a dryland's soil respiration and relationships with climate, whole plant photosynthesis and soil fertility
Authors: Wertin Timothy M. , Young Kristina , Reed Sasha C.
Published: March 2018

Arid and semiarid ecosystems play a significant role in regulating global carbon cycling, yet our understanding of the controls over the dominant pathways of dryland CO2 exchange remains poor. Substantial amounts of dryland soil are not covered by vascular plants and this patchiness in cover has important implications for spatial patterns and controls of carbon cycling. Spatial variation in soil respiration has been attributed to variation in soil moisture, temperature, nutrients and rhizodeposition, while seasonal patterns have been attributed to changes in moisture, temperature and photosynthetic inputs belowground. To characterize how controls over respiration vary spatially and temporally in a dryland ecosystem and to concurrently explore multiple potential controls, we estimated whole plant net photosynthesis (Anet) and soil respiration at four distances from the plant base, as well as corresponding fine root biomass and soil carbon and nitrogen pools, four times during a growing season. To determine if the controls vary between different plant functional types for Colorado Plateau species, measurements were made on the C4 shrub, Atriplex confertifolia, and C3 grass, Achnatherum hymenoides. Soil respiration declined throughout the growing season and diminished with distance from the plant base, though variations in both were much smaller than expected. The strongest relationship was between soil respiration and soil moisture. Soil respiration was correlated with whole plant Anet, although the relationship varied between species and distance from plant base. In the especially dry year of this study we did not observe any consistent correlations between soil respiration and soil carbon or nitrogen pools. Our findings suggest that abiotic factors, especially soil moisture, strongly regulate the response of soil respiration to biotic factors and soil carbon and nitrogen pools in dryland communities and, at least in dry years, may override expected spatial and seasonal patterns.
Evidence for heterochrony in the cranial evolution of fossil crocodyliforms
Authors: Godoy Pedro L. , Ferreira Gabriel S. , Montefeltro Felipe C. , Vila Nova Bruno C. , Butler Richard J. , Langer Max C.
Published: March 2018

The southern supercontinent of Gondwana was home to an extraordinary diversity of stem‐crocodylians (Crocodyliformes) during the Late Cretaceous. The remarkable morphological disparity of notosuchian crocodyliforms indicates that this group filled a wide range of ecological roles more frequently occupied by other vertebrates. Among notosuchians, the distinctive cranial morphology and large body sizes of Baurusuchidae suggest a role as apex predators in ecosystems in which the otherwise dominant predatory theropod dinosaurs were scarce. Large‐bodied crocodyliforms, modern and extinct, are known to have reached large sizes by extending their growth period. In a similar way, peramorphic heterochronic processes may have driven the evolution of the similarly large baurusuchids. To assess the presence of peramorphic processes in the cranial evolution of baurusuchids, we applied a geometric morphometric approach to investigate ontogenetic cranial shape variation in a comprehensive sample of notosuchians. Our results provide quantitative morphological evidence that peramorphic processes influenced the cranial evolution of baurusuchids. After applying size and ancestral ontogenetic allometry corrections to our data, we found no support for the action of either hypermorphosis or acceleration, indicating that these two processes alone cannot explain the shape variation observed in Notosuchia. Nevertheless, the strong link between cranial shape variation and size increase in baurusuchids suggests that peramorphic processes were involved in the emergence of hypercarnivory in these animals. Our findings illustrate the role of heterochrony as a macroevolutionary driver, and stress, once more, the usefulness of geometric morphometric techniques for identifying heterochronic processes behind evolutionary trends.
Moral judgment toward relationship betrayals and those who commit them
Authors: SELTERMAN DYLAN , MOORS AMY C. , KOLEVA SPASSENA
Published: March 2018

In three experimental studies (total N = 1,056), we examined moral judgments toward relationship betrayals, and how these judgments depended on whether characters and their actions were perceived to be pure and loyal compared to the level of harm caused. In Studies 1 and 2, the focus was on confessing a betrayal, whereas in Study 3, the focus was on the act of sexual infidelity. Perceptions of harm/care were inconsistently and less strongly associated with moral judgment toward the behavior or the character, relative to perceptions of purity and loyalty, which emerged as key predictors of moral judgment across all studies. Our findings demonstrate that a diversity of cognitive factors play a key role in the moral perception of relationship betrayals.
The Emotion Mapping Activity: Preliminary evaluation of a mindfulness‐informed exercise to improve emotion labeling in alexithymic persons
Authors: Edwards Emily , Shivaji Sindhuja , Wupperman Peggilee
Published: March 2018

Alexithymia is a psychoemotional trait associated with many treatment‐resistant psychological and social difficulties. Research suggests that these difficulties stem primarily from an inability to appropriately apply linguistic labels to emotional experiences and content. The present research introduces and preliminarily evaluates a novel mindfulness‐informed exercise to improve emotion‐labeling ability in alexithymic persons. Based in culturally universal patterns of somatic experience, the Emotion Mapping Activity (EMA) directs alexithymic persons to reflect on their internal, somatic experiences as a source of information for interpreting and labeling emotional experiences. In the present study, 67 alexithymic persons completed a series of emotion‐labeling tasks either with or without assistance of the EMA. Results suggest that completion of the EMA may improve ability to label emotions that would be otherwise misinterpreted – without interfering with labeling that is already intact. Though further research is necessary, the present study suggests that the EMA may hold the potential to be incorporated into psychotherapy protocols as an exercise for improving emotion‐labeling ability in alexithymic clients.
Spatial and temporal patterns of fires in tropical savannas of Indonesia
Authors: Sutomo  , van Etten Eddie
Published: March 2018

This paper examines spatial and temporal patterns of large to medium‐sized fires across the Indonesian Archipelago using remote sensing, particularly the MODIS fire products, over a 14 years period (2000–13 inclusive) in conjunction with climatic and land data in a GIS. Results showed fires (burned area and number of fires) were detected the most in year 2002 and least in 2010. The extent of burning was correlated with the annual Southern Oscillation Index with most burning occurring during times of sustained negative SOI values, which generally means drier conditions across the region. Most of the detected fires occurred in the middle of the dry season and in drier eastern Indonesia. Across Indonesia, approximately 1.5 per cent of available open vegetation area burned, whereas only 0.5 per cent of forest area burned. Most open vegetation burning was detected in the savanna with an area equivalent to 11.1 per cent of its extent being burned over the 14 years. On Sumba Island, where the pronounced dry season extends for at least four months, open vegetation is the most common land cover type, of which 99 per cent burned by area over the study period making it the island with the most burned areas in the Indonesian Archipelago.
Serological surveillance for Tahyna virus (California encephalitis orthobunyavirus, Peribunyaviridae) neutralizing antibodies in wild ungulates in Austria, Hungary and Romania
Authors: Camp J. V. , Haider R. , Porea D. , Oslobanu L. E. , Forgách P. , Nowotny N.
Published: March 2018

A serosurvey for Tahyna virus (TAHV), a mosquito‐borne California encephalitis orthobunyavirus (Peribunyaviridae) endemic to Europe, was performed to estimate the activity of TAHV on a broad geographic scale. Sera from wild boar (Sus scrofa), roe deer (Capreolus capreolus) and red deer (Cervus elaphus) were collected from Austria, Hungary and Romania. Samples were tested for neutralizing antibodies against TAHV using a virus microneutralization assay. The results demonstrate that TAHV transmission to mammals is widespread in Europe, particularly in the wild boar population where the mean rate of seroconversion is 15.2%.
Family-oriented interventions for adults with acquired brain injury and their families: a scoping review protocol
Authors: de Goumoëns Véronique , Marques Rio Laura , Ramelet Anne-Sylvie
Published: March 2018

Review question:

The aim of this scoping review is to examine the range and nature of family-oriented interventions that have been developed and/or tested for people with acquired brain injuries (ABI) and their families in all settings. Specifically the review questions are:

What are the aims and characteristics (type, delivery mode and duration, provider) of family-oriented interventions available for people with ABI and their families?

What types of outcomes have been reported in the literature when testing or implementing family-oriented interventions?
Effectiveness of four-factor prothrombin complex concentrates versus plasma on vitamin K antagonist associated plasma international normalized ratio reversal: a systematic review protocol
Authors: McPhail Andrew , Jokel Dominick
Published: March 2018

Review question:

The question of this review is: what is the effectiveness of Kcentra/Beriplex/Confidex compared to plasma for international normalized ratio (INR) reduction in adult patients (18 years and over) on any vitamin K antagonist therapy?
Caregivers’ experiences of feeding children with cerebral palsy: a systematic review protocol of qualitative evidence
Authors: Taylor Christine , Zhang Melissa , Foster Jann , Novak Iona , Badawi Nadia
Published: March 2018

Review question/objective:

The overall objective of this systematic review is to identify, critically appraise and synthesize the literature regarding the feeding experiences of caregivers who care for children with cerebral palsy. The specific review question is: What are the experiences of caregivers feeding children with cerebral palsy?
Primate fetal hepatic responses to maternal obesity: epigenetic signalling pathways and lipid accumulation
Authors: Puppala Sobha , Li Cun , Glenn Jeremy P. , Saxena Romil , Gawrieh Samer , Quinn Amy , Palarczyk Jennifer , Dick Edward J. , Nathanielsz Peter W. , Cox Laura A.
Published: March 2018

Key points

Maternal obesity (MO) and exposure to a high‐fat, high‐simple‐carbohydrate diet during pregnancy predisposes offspring to obesity, metabolic and cardiovascular disorders in later life.

Underlying molecular pathways and potential epigenetic factors that are dysregulated in MO were identified using unbiased transcriptomic methods.

There was increased lipid accumulation and severe steatosis in the MO baboon fetal liver suggesting that these offspring are on an early trajectory of non‐alcoholic fatty liver disease and non‐alcoholic steatohepatitis.

Maternal obesity (MO) increases offspring cardiometabolic disease risk. Altered fetal liver development in response to the challenge of MO has metabolic consequences underlying adverse offspring life‐course health outcomes. Little is known about the molecular pathways and potential epigenetic changes regulating primate fetal liver responses to MO. We hypothesized that MO would induce fetal baboon liver epigenetic changes resulting in dysregulation of key metabolic pathways that impact lipid metabolism. MO was induced prior to pregnancy by a high‐fat, high‐fructose diet. Unbiased gene and microRNA (small RNA Seq) abundance analyses were performed on fetal baboon livers at 0.9 gestation and subjected to pathway analyses to identify fetal liver molecular responses to MO. Fetal baboon liver lipid and glycogen content were quantified by the Computer Assisted Stereology Toolbox. In response to MO, fetal livers revealed dysregulation of TCA cycle, proteasome, oxidative phosphorylation, glycolysis and Wnt/β‐catenin signalling pathways together with marked lipid accumulation supporting our hypothesis that multiple pathway dysregulation detrimentally impacts lipid management. This is the first study of MO programming of the non‐human primate fetal liver using unbiased transcriptome analysis to detect changes in hepatic gene expression levels and identify potential microRNA epigenetic regulators of metabolic disruption.
Study undercuts claims of new neurons in adult brains
Authors: Underwood Emily
Published: March 2018

Other groups still see evidence for lifelong neurogenesis.
Looking for love
Authors: Cornwall Warren
Published: March 2018

South Asia's "vulture safe zones" aim to preserve, and win respect for, a vital scavenger.
Nascent DNA methylome mapping reveals inheritance of hemimethylation at CTCF/cohesin sites
Authors: Xu Chenhuan , Corces Victor G.
Published: March 2018

Hemimethylation drives chromatin assembly

Cytosine DNA methylation is a heritable and essential epigenetic mark. During DNA replication, cytosines on mother strands remain methylated, but those on daughter strands are initially unmethylated. These hemimethylated sites are rapidly methylated to maintain faithful methylation patterns. Xu and Corces mapped genome-wide strand-specific DNA methylation sites on nascent chromatin, confirming such maintenance in the vast majority of the DNA methylome (see the Perspective by Sharif and Koseki). However, they also identified a small fraction of sites that were stably hemimethylated and showed their inheritance at CTCF (CCCTC-binding factor)/cohesin binding sites. These inherited hemimethylation sites were required for CTCF and cohesin to establish proper chromatin interactions.

Science
, this issue p.
1166
; see also p.
1102
Photoperiodic control of seasonal growth is mediated by ABA acting on cell-cell communication
Authors: Tylewicz S. , Petterle A. , Marttila S. , Miskolczi P. , Azeez A. , Singh R. K. , Immanen J. , Mähler N. , Hvidsten T. R. , Eklund D. M. , Bowman J. L. , Helariutta Y. , Bhalerao R. P.
Published: March 2018

Dormancy by communication shutdown

Trees become dormant in winter, with encapsulated buds protected against harsh conditions. Tylewicz
et al.
found that, as the days get shorter, communication channels between cells in aspen trees shut down. The blocked plasmodesmata sequester the dormant meristems from growth signals. Growth-promoting signals can be turned on and off relatively rapidly, but the closed plasmodesmata are not so nimble. Thus, despite the occasional sunny day, the trees stay dormant until spring.

Science
, this issue p.
212
The science of fake news
Authors: Lazer David M. J. , Baum Matthew A. , Benkler Yochai , Berinsky Adam J. , Greenhill Kelly M. , Menczer Filippo , Metzger Miriam J. , Nyhan Brendan , Pennycook Gordon , Rothschild David , Schudson Michael , Sloman Steven A. , Sunstein Cass R. , Thorson Emily A. , Watts Duncan J. , Zittrain Jonathan L.
Published: March 2018

Addressing fake news requires a multidisciplinary effort
Ice-VII inclusions in diamonds: Evidence for aqueous fluid in Earth’s deep mantle
Authors: Tschauner O. , Huang S. , Greenberg E. , Prakapenka V. B. , Ma C. , Rossman G. R. , Shen A. H. , Zhang D. , Newville M. , Lanzirotti A. , Tait K.
Published: March 2018

Encapsulating Earth's deep water filter

Small inclusions in diamonds brought up from the mantle provide valuable clues to the mineralogy and chemistry of parts of Earth that we cannot otherwise sample. Tschauner
et al.
found inclusions of the high-pressure form of water called ice-VII in diamonds sourced from between 410 and 660 km depth, the part of the mantle known as the transition zone. The transition zone is a region where the stable minerals have high water storage capacity. The inclusions suggest that local aqueous pockets form at the transition zone boundary owing to the release of chemically bound water as rock cycles in and out of this region.

Science
, this issue p.
1136
Coherent, atomically thin transition-metal dichalcogenide superlattices with engineered strain
Authors: Xie Saien , Tu Lijie , Han Yimo , Huang Lujie , Kang Kibum , Lao Ka Un , Poddar Preeti , Park Chibeom , Muller David A. , DiStasio Robert A. , Park Jiwoong
Published: March 2018

Coherent strained superlattices

Two-dimensional superlattices represent the atomic-thickness limit of heterostructures that enable technologies such as strain-engineered multiferroics and quantum-cascade lasers. Xie
et al.
were able to produce monolayer superlattices of transition metal dichalcogenides (WS
2
and WSe
2
) with full lattice coherence, despite a 4% lattice mismatch. They used a modulated metal-organic chemical vapor deposition process that precisely controlled each precursor. Furthermore, the authors could strain-engineer the optical properties of the superlattices to observe out-of-plane rippling.

Science
, this issue p.
1131
The spread of true and false news online
Authors: Vosoughi Soroush , Roy Deb , Aral Sinan
Published: March 2018

Lies spread faster than the truth

There is worldwide concern over false news and the possibility that it can influence political, economic, and social well-being. To understand how false news spreads, Vosoughi
et al.
used a data set of rumor cascades on Twitter from 2006 to 2017. About 126,000 rumors were spread by ∼3 million people. False news reached more people than the truth; the top 1% of false news cascades diffused to between 1000 and 100,000 people, whereas the truth rarely diffused to more than 1000 people. Falsehood also diffused faster than the truth. The degree of novelty and the emotional reactions of recipients may be responsible for the differences observed.

Science
, this issue p.
1146
Structure of the nuclear exosome captured on a maturing preribosome
Authors: Schuller Jan Michael , Falk Sebastian , Fromm Lisa , Hurt Ed , Conti Elena
Published: March 2018

The RNA exosome captured in action

The RNA exosome, a major RNA degradation machine, processes ribosomal RNA (rRNA) precursors and is directly coupled to the protein synthesis machine, the ribosome. Using cryo–electron microscopy, Schuller
et al.
investigated the structure of the precursor large ribosomal subunit from yeast with unprocessed rRNA in complex with the RNA exosome. The structure captures a snapshot of two molecular machines transiently interacting and explains how the RNA exosome acts on an authentic physiological substrate and remodels the large subunit during ribosome maturation.

Science
, this issue p.
219
Structural basis for coupling protein transport and N-glycosylation at the mammalian endoplasmic reticulum
Authors: Braunger Katharina , Pfeffer Stefan , Shrimal Shiteshu , Gilmore Reid , Berninghausen Otto , Mandon Elisabet C. , Becker Thomas , Förster Friedrich , Beckmann Roland
Published: March 2018

A close-up view of oligosaccharyltransferase

Many secretory and membrane proteins are modified through the attachment of sugar chains by N-glycosylation. Such modification is required for correct protein folding, targeting, and functionality. In mammalian cells, N-glycosylation is catalyzed by the oligosaccharyltransferase (OST) complex via its STT3 subunit. OST forms a complex with the ribosome and the Sec61 protein translocation channel. Braunger
et al.
combined cryo–electron microscopy approaches to visualize mammalian ribosome-Sec61-OST complexes in order to build an initial molecular model for mammalian OST.

Science
, this issue p.
215
Behind the scenes of the built environment
Built: The Hidden Stories Behind Our Structures
Roma Agrawal
Bloomsbury, 2018. 308 pp.
Authors: Riley Donna
Published: March 2018

An approachable introduction to structural engineering entertains and inspires
Hemimethylation: DNA's lasting odd couple
Authors: Sharif Jafar , Koseki Haruhiko
Published: March 2018

Stably inherited DNA hemimethylation regulates chromatin interaction and transcription
Building better bile ducts
Authors: Sampaziotis Fotios
Published: March 2018

An organoid-based model promises to improve our understanding of bile duct disorders
Toward a true cure for hearing impairment
Authors: McLean Will
Published: March 2018

The regenerative power of progenitor cells holds promise for reversing hearing loss
Imidazolopiperazines Kill both Rings and Dormant Rings in Wild-Type and K13 Artemisinin-Resistant Plasmodium falciparum In Vitro
Authors: Dembele Laurent , Gupta Devendra Kumar , Lim Michelle Yi-Xiu , Ang Xiaoman , Selva Jeremy J. , Chotivanich Kesinee , Nguon Chea , Dondorp Arjen M. , Bonamy Ghislain M. C. , Diagana Thierry T. , Bifani Pablo
Published: March 2018

Artemisinin (ART) resistance has spread through Southeast Asia, posing a serious threat to the control and elimination of malaria. ART resistance has been associated with mutations in the
Plasmodium falciparum
kelch-13 (
Pfk13
) propeller domain. Phenotypically, ART resistance is defined as delayed parasite clearance in patients due to the reduced susceptibility of early ring-stage parasites to the active metabolite of ART dihydroartemisinin (DHA). Early rings can enter a state of quiescence upon DHA exposure and resume growth in its absence. These quiescent rings are referred to as dormant rings or DHA-pretreated rings (here called dormant rings). The imidazolopiperazines (IPZ) are a novel class of antimalarial drugs that have demonstrated efficacy in early clinical trials. Here, we characterized the stage of action of the IPZ GNF179 and evaluated its activity against rings and dormant rings in wild-type and ART-resistant parasites. Unlike DHA, GNF179 does not induce dormancy. We show that GNF179 is more rapidly cidal against schizonts than against ring and trophozoite stages. However, with 12 h of exposure, the compound effectively kills rings and dormant rings of both susceptible and ART-resistant parasites within 72 h. We further demonstrate that in combination with ART, GNF179 effectively prevents recrudescence of dormant rings, including those bearing
pfk13
propeller mutations.
Population Pharmacokinetics of Meropenem in Plasma and Subcutis from Patients on Extracorporeal Membrane Oxygenation Treatment
Authors: Hanberg Pelle , Öbrink-Hansen Kristina , Thorsted Anders , Bue Mats , Tøttrup Mikkel , Friberg Lena E. , Hardlei Tore Forsingdal , Søballe Kjeld , Gjedsted Jakob
Published: March 2018

The objectives of this study were to describe meropenem pharmacokinetics (PK) in plasma and/or subcutaneous adipose tissue (SCT) in critically ill patients receiving extracorporeal membrane oxygenation (ECMO) treatment and to develop a population PK model to simulate alternative dosing regimens and modes of administration. We conducted a prospective observational study. Ten patients on ECMO treatment received meropenem (1 or 2 g) intravenously over 5 min every 8 h. Serial SCT concentrations were determined using microdialysis and compared with plasma concentrations. A population PK model of SCT and plasma data was developed using NONMEM. Time above clinical breakpoint MIC for
Pseudomonas aeruginosa
(8 mg/liter) was predicted for each patient. The following targets were evaluated: time for which the free (unbound) concentration is maintained above the MIC of at least 40% (40%
f
T>MIC), 100%
f
T>MIC, and 100%
f
T>4×MIC. For all dosing regimens simulated in both plasma and SCT, 40%
f
T>MIC was attained. However, prolonged meropenem infusion would be needed for 100%
f
T>MIC and 100%
f
T>4×MIC to be obtained. Meropenem plasma and SCT concentrations were associated with estimated creatinine clearance (eCL
Cr
). Simulations showed that in patients with increased eCL
Cr
, dose increment or continuous infusion may be needed to obtain therapeutic meropenem concentrations. In conclusion, our results show that using traditional targets of 40%
f
T>MIC for standard meropenem dosing of 1 g intravenously every 8 h is likely to provide sufficient meropenem concentration to treat the problematic pathogen
P. aeruginosa
for patients receiving ECMO treatment. However, for patients with an increased eCL
Cr
, or if more aggressive targets, like 100%
f
T>MIC or 100%
f
T>4×MIC, are adopted, incremental dosing or continuous infusion may be needed.
Inactivation of the Pseudomonas-Derived Cephalosporinase-3 (PDC-3) by Relebactam
Authors: Barnes Melissa D. , Bethel Christopher R. , Alsop Jim , Becka Scott A. , Rutter Joseph D. , Papp-Wallace Krisztina M. , Bonomo Robert A.
Published: March 2018

Pseudomonas aeruginosa
is a prevalent and life-threatening Gram-negative pathogen.
Pseudomonas
-derived cephlosporinase (PDC) is the major inducible cephalosporinase in
P. aeruginosa
. In this investigation, we show that relebactam, a diazabicyclooctane β-lactamase inhibitor, potently inactivates PDC-3, with a
k
2
/
K
of 41,400 M
−1
s
−1
and a
k
off
of 0.00095 s
−1
. Relebactam restored susceptibility to imipenem in 62% of multidrug-resistant
P. aeruginosa
clinical isolates, while only 21% of isolates were susceptible to imipenem-cilastatin alone. Relebactam promises to increase the efficacy of imipenem-cilastatin against
P. aeruginosa
.
Microbiome Dynamics in a Large Artificial Seawater Aquarium
Authors: Patin Nastassia V. , Pratte Zoe A. , Regensburger Matthew , Hall Eric , Gilde Kailen , Dove Alistair D. M. , Stewart Frank J.
Published: March 2018

Artificial habitats for animals have high commercial and societal value. Microbial communities (microbiomes) in such habitats may play ecological roles similar to those in nature. However, this hypothesis remains largely untested. Georgia Aquarium's
Ocean Voyager
(OV) exhibit is a closed-system aquatic habitat that mimics the oligotrophic open ocean and houses thousands of large marine animals, including fish, sea turtles, and whale sharks. We present a 14-month time series characterizing the OV water column microbiome. The composition and stability of the microbiome differed from those of natural marine environments with similar chemical features. The composition shifted dramatically over the span of 2 weeks and was characterized by bloom events featuring members of two heterotrophic bacterial lineages with cosmopolitan distributions in the oceans. The relative abundances of these lineages were inversely correlated, suggesting an overlap in ecological niches. Transcript mapping to metagenome-assembled genomes (MAGs) of these taxa identified unique characteristics, including the presence and activity of genes for the synthesis and degradation of cyanophycin, an amino acid polymer linked to environmental stress and found frequently in cyanobacteria but rarely in heterotrophic bacteria. The dominant MAGs also contained and transcribed plasmid-associated sequences, suggesting a role for conjugation in adaptation to the OV environment. These findings indicate a highly dynamic microbiome despite the stability of the physical and chemical parameters of the water column. Characterizing how such fluctuations affect microbial function may inform our understanding of animal health in closed aquaculture systems.

IMPORTANCE
Public aquariums play important societal roles, for example, by promoting science education and helping conserve biodiversity. The health of aquarium animals depends on interactions with the surrounding microbiome. However, the extent to which aquariums recreate a stable and natural microbial ecosystem is uncertain. This study describes the taxonomic composition of the water column microbiome over 14 months in a large indoor aquatic habitat, the
Ocean Voyager
exhibit at the Georgia Aquarium. Despite stable water column conditions, the exhibit experienced blooms in which the abundance of a single bacterial strain increased to over 65% of the community. Genome analysis indicated that the OV's dominant strains share unique adaptations, notably genes for storage polymers associated with environmental stress. These results, interpreted alongside data from natural ocean systems and another artificial seawater aquarium, suggest a highly dynamic aquarium microbiome and raise questions of how microbiome stability may affect the ecological health of the habitat.
Landscape-Scale Factors Affecting the Prevalence of Escherichia coli in Surface Soil Include Land Cover Type, Edge Interactions, and Soil pH
Authors: Dusek Nicholas , Hewitt Austin J. , Schmidt Kaycie N. , Bergholz Peter W.
Published: March 2018

Escherichia coli
is deposited into soil with feces and exhibits subsequent population decline with concomitant environmental selection. Environmentally persistent strains exhibit longer survival times during this selection process, and some strains have adapted to soil and sediments. A georeferenced collection of
E. coli
isolates was developed comprising 3,329 isolates from 1,428 soil samples that were collected from a landscape spanning the transition from the grasslands to the eastern deciduous forest biomes. The isolate collection and sample database were analyzed together to discover how land cover, site characteristics, and soil chemistry influence the prevalence of cultivable
E. coli
in surface soil. Soils from forests and pasture lands had equally high prevalences of
E. coli
. Edge interactions were also observed among land cover types, with proximity to forests and pastures affecting the likelihood of
E. coli
isolation from surrounding soils.
E. coli
is thought to be more prevalent in sediments with high moisture, but this was observed only in grass- or crop-dominated lands in this study. Because differing
E. coli
phylogroups are thought to have differing ecology profiles, isolates were also typed using a novel single-nucleotide polymorphism (SNP) genotyping assay. Phylogroup B1 was the dominant group isolated from soil, as has been reported in all other surveys of environmental
E. coli
. Although differences were small, isolates belonging to phylogroups B2 and D were associated with wooded areas, slightly more acidic soils, and soil sampling after rainfall events. In contrast, isolates from phylogroups B1 and E were associated with pasture lands.

IMPORTANCE
The consensus is that complex niches or life cycles should select for complex genomes in organisms. There is much unexplained biodiversity in
E. coli
, and its cycling through complex extrahost environments may be a cause. In order to understand the evolutionary processes that lead to adaptation for survival and growth in soil, an isolate collection that associates soil conditions and isolate genome sequences is required. An equally important question is whether traits selected in soil or other extrahost habitats can be transmitted to
E. coli
residing in hosts via gene flow. The new findings about the distribution of
E. coli
in soil at the landscape scale (i) enhance our capability to study how extrahost environments influence the evolution of
E. coli
and other bacteria, (ii) advance our knowledge of the environmental biology of this microbe, and (iii) further affirm the emerging scientific consensus that
E. coli
in waterways originates from nonpoint sources not associated with human activity or livestock farming.
Two Phytoplasmas Elicit Different Responses in the Insect Vector Euscelidius variegatus Kirschbaum
Authors: Galetto Luciana , Abbà Simona , Rossi Marika , Vallino Marta , Pesando Massimo , Arricau-Bouvery Nathalie , Dubrana Marie-Pierre , Chitarra Walter , Pegoraro Mattia , Bosco Domenico , Marzachì Cristina
Published: March 2018

Phytoplasmas are plant-pathogenic bacteria transmitted by hemipteran insects. The leafhopper
Euscelidius variegatus
is a natural vector of chrysanthemum yellows phytoplasma (CYp) and a laboratory vector of flavescence dorée phytoplasma (FDp). The two phytoplasmas induce different effects on this species: CYp slightly improves whereas FDp negatively affects insect fitness. To investigate the molecular bases of these different responses, transcriptome sequencing (RNA-seq) analysis of
E. variegatus
infected with either CYp or FDp was performed. The sequencing provided the first
de novo
transcriptome assembly for a phytoplasma vector and a starting point for further analyses on differentially regulated genes, mainly related to immune system and energy metabolism. Insect phenoloxidase activity, immunocompetence, and body pigmentation were measured to investigate the immune response, while respiration and movement rates were quantified to confirm the effects on energy metabolism. The activation of the insect immune response upon infection with FDp, which is not naturally transmitted by
E. variegatus
, confirmed that this bacterium is mostly perceived as a potential pathogen. Conversely, the acquisition of CYp, which is naturally transmitted by
E. variegatus
, seems to increase the insect fitness by inducing a prompt response to stress. This long-term relationship is likely to improve survival and dispersal of the infected insect, thus enhancing the opportunity of phytoplasma transmission.
Serum Amyloid P and IgG Exhibit Differential Capabilities in the Activation of the Innate Immune System in Response to Bacillus anthracis Peptidoglycan
Authors: Girton Alanson W. , Popescu Narcis I. , Keshari Ravi S. , Burgett Tarea , Lupu Florea , Coggeshall K. Mark
Published: March 2018

We showed that human IgG supported the response by human innate immune cells to peptidoglycan (PGN) fromBacillus anthracisand PGN-induced complement activation. However, other serum constituents have been shown to interact with peptidoglycan, including the IgG-like soluble pattern recognition receptor serum amyloid P (SAP). Here, we compared the abilities of SAP and of IgG to support monocyte and complement responses to PGN. Utilizingin vitromethods, we demonstrate that SAP is superior to IgG in supporting monocyte production of cytokines in response to PGN. Like IgG, the response supported by SAP was enhanced by phagocytosis and signaling kinases, such as Syk, Src, and phosphatidylinositol 3-kinase, that are involved in various cellular processes, including Fc receptor signaling. Unlike IgG, SAP had no effect on the activation of complement in response to PGN. These data demonstrate an opsonophagocytic role for SAP in response to PGN that propagates a cellular response without propagating the formation of the terminal complement complex.
Visible DNA Microarray System as an Adjunctive Molecular Test in Identification of Pathogenic Fungi Directly from a Blood Culture Bottle
Authors: Sturaro Lais Lovison , Gonoi Tohru , Busso-Lopes Ariane Fidelis , Tararam Cibele Aparecida , Levy Carlos Emilio , Lyra Luzia , Trabasso Plinio , Schreiber Angélica Zaninelli , Kamei Katsuhiko , Moretti Maria Luiza
Published: March 2018

A DNA microarray platform, based on the nucleotide sequences of the internal transcribed spacer regions (ITS1 and ITS2) of the rRNA gene, was developed to identify 32 fungal pathogens at the species level. The probe sequences were spotted onto polycarbonate slides with a mini-microarray printer, and after the hybridization, the results were visible with the naked eye. The performance of the microarray platform was evaluated against the commercial automated systems (Vitek 2 and BD Phoenix systems) and DNA sequencing (gold standard). A total of 461 blood culture bottles were tested: 127 positive for fungi, 302 positive for bacteria, and 32 that were negative. Once the microorganisms were identified by automated systems, fungal DNA was extracted directly from the blood culture bottles. The DNA products were tested using the microarray platform, and DNA sequencing was performed. The results of the microarray and DNA sequencing were concordant in 96.7% of cases, and the results from the automated systems and DNA sequencing were concordant in 98.4%. Of all the nucleotide sequences contained in the microarray platform, the microarray failed to identify four fungal isolates (one
Candida parapsilosis
, two
Candida tropicalis
, and one
Cryptococcus neoformans
). Of note, the microarray detected
Candida krusei
DNA in two blood cultures from the same patient, whereas the automated system was only positive for
Enterococcus faecium
. Our microarray system provided reliable and fast fungal identification compared to that from DNA sequencing and the automated systems. The simplicity of reading the results by the naked eye made this DNA platform a suitable method for fungal molecular diagnosis.
Identification of H209 as Essential for pH 8-Triggered Receptor-Independent Syncytium Formation by S Protein of Mouse Hepatitis Virus A59
Authors: Li Pei , Shan Yiwei , Zheng Wangliang , Ou Xiuyuan , Mi Dan , Mu Zhixia , Holmes Kathryn V. , Qian Zhaohui
Published: March 2018

The spike glycoprotein (S) of murine coronavirus mouse hepatitis virus (MHV) strain A59 uses murine carcinoembryonic antigen-related cell adhesion molecule 1a as its receptor for cell entry, but S protein can also be triggered in the absence of receptor by pH 8.0 alone at 37°C. The mechanism by which conformational changes of this S glycoprotein can be triggered by pH 8.0 has not yet been determined. Here, we show that MHV-A59 S protein is triggered by pH 8.0 at 37°C to induce receptor-independent syncytium (RIS) formation on 293T cells, and that the conformational changes in S proteins triggered by pH 8.0 are very similar to those triggered by receptor binding. We systemically mutated each of 15 histidine residues in S protein and found that H209 is essential for pH 8.0-triggered RIS formation, while H179, H441, H643, and H759 also play important roles in this process. Replacement of H209 with Ala had no effect on receptor binding, but in murine 17Cl.1 cells mutant H209A MHV-A59 showed delayed growth kinetics and was readily outcompeted by wild-type virus when mixed together, indicating that the H209A mutation caused a defect in virus fitness. Finally, the H209A mutation significantly increased the thermostability of S protein in its prefusion conformation, which may raise the energy barrier for conformational change of S protein required for membrane fusion and lead to a decrease in virus fitness in cell culture. Thus, MHV-A59 may have evolved to lower the stability of its S protein in order to increase virus fitness.

IMPORTANCE
Enveloped viruses enter cells through fusion of viral and cellular membranes, and the process is mediated by interactions between viral envelope proteins and their host receptors. In the prefusion conformation, viral envelope proteins are metastable, and activation to the fusion conformation is tightly regulated, since premature activation would lead to loss of viral infectivity. The stability of viral envelope proteins greatly influences their activation and virus fitness. Here, we report that, similar to the A82V mutation in Ebola glycoprotein, in the S glycoprotein of murine coronavirus MHV-A59, the histidine residue at position of 209 significantly affects the thermal stability of the S protein, determines whether S protein can be activated at 37°C by either pH 8.0 alone or by receptor binding, and affects viral fitness in cell culture. Thus, the spike glycoprotein of MHV-A59 has evolved to retain histidine at position 209 to optimize virus fitness.
Ethnicity and sexual risk in heterosexual people attending sexual health clinics in England: a cross-sectional, self-administered questionnaire study
Authors: Coyle Rachel Margaret , Miltz Ada Rose , Lampe Fiona C , Sewell Janey , Phillips Andrew N , Speakman Andrew , Dhar Jyoti , Sherr Lorraine , Sadiq S Tariq , Taylor Stephen , Ivens Daniel R , Collins Simon , Elford Jonathan , Anderson Jane , Rodger Alison
Published: March 2018

Objectives

In the UK, people of black ethnicity experience a disproportionate burden of HIV and STI. We aimed to assess the association of ethnicity with sexual behaviour and sexual health among women and heterosexual men attending genitourinary medicine (GUM) clinics in England.

Methods

The Attitudes to and Understanding of Risk of Acquisition of HIV is a cross-sectional, self-administered questionnaire study of HIV negative people recruited from 20 GUM clinics in England, 2013–2014. Modified Poisson regression with robust SEs was used to calculate adjusted prevalence ratios (aPR) for the association between ethnicity and various sexual risk behaviours, adjusted for age, study region, education and relationship status.

Results

Questionnaires were completed by 1146 individuals, 676 women and 470 heterosexual men. Ethnicity was recorded for 1131 (98.8%) participants: 550 (48.6%) black/mixed African, 168 (14.9%) black/mixed Caribbean, 308 (27.2%) white ethnic groups, 105 (9.3%) other ethnicity. Compared with women from white ethnic groups, black/mixed African women were less likely to report condomless sex with a non-regular partner (aPR (95% CI) 0.67 (0.51 to 0.88)), black/mixed African and black/mixed Caribbean women were less likely to report two or more new partners (0.42 (0.32 to 0.55) and 0.44 (0.29 to 0.65), respectively), and black/mixed Caribbean women were more likely to report an STI diagnosis (1.56 (1.00 to 2.42)). Compared with men from white ethnic groups, black/mixed Caribbean men were more likely to report an STI diagnosis (1.91 (1.20 to 3.04)), but did not report risk behaviours more frequently. Men and women of black/mixed Caribbean ethnicity remained more likely to report STI history after adjustment for sexual risk behaviours.

Discussion

Risk behaviours were reported less frequently by women of black ethnicity; however, history of STI was more prevalent among black/mixed Caribbean women. In black/mixed Caribbean men, higher STI history was not explained by ethnic variation in reported risk behaviours. The association between STI and black/mixed Caribbean ethnicity remained after adjustment for risk behaviours.