bluuebunny/crossref_metadata_2025 huggingface dataset:
N-chlorotaurine Inactivates Acanthamoeba and Candida albicans in the Porcine Ex Vivo Corneal Infection Model
Authors: Teuchner Barbara , Wibmer Idris D. , Schaumann Philipp , Seifarth Christof , Walochnik Julia , Nagl Markus
Published: April 2019

Purpose:

N-chlorotaurine (NCT) is an anti-infective belonging to the class of chloramines and an investigative drug for the topical treatment of keratoconjunctivitis. The aim of the present study was to demonstrate its efficacy against Acanthamoeba and Candida in corneas infected ex vivo.

Methods:

Corneal buttons from porcine eyes were contaminated with Acanthamoeba castellanii trophozoites or Candida albicans Centraalbureau voor Schimmelcultures 5982 and incubated for 7 and 3 days, respectively. Subsequently, they were treated with 1% NCT for 5 to 120 minutes. After further incubation for 2 days in the absence of NCT in tests with A. castellanii, the buttons were homogenized, and the amoebae grown for a further 5 days before they were counted in a light microscope. For C. albicans, quantitative cultures were performed from corneal homogenates.

Results:

Incubation of 120 minutes in NCT completely inhibited the regrowth of A. castellanii and reduced the number of C. albicans colony-forming unit counts by 4 log10. In addition, at 60 minutes, significant reductions of both pathogens could be observed. Histology showed penetration of pathogens into the stroma of the corneal buttons.

Conclusions:

NCT inactivates A. castellanii and C. albicans in corneal tissue.
Mycobacterium Avium Complex Presenting as Pulmonary Nodules in a Child With Sickle Cell Disease
Authors: Pham Thu Anh , Samuel Linh Thuy , Lefevre Cassandra , Mallett Lea H. , Sagar Malvika
Published: April 2019

The case of a 10-year-old child with sickle cell disease with pulmonary nodules and prolonged fevers is reported here. The child was first diagnosed with sarcoidosis based on lung biopsy, but unresponsiveness to therapy led to a second lung biopsy, which revealed the true diagnosis of mycobacterium avium complex disease. Multiple possible explanations for why the patient became infected exist. The patient was baseline immunocompromised due to her sickle cell disease, was exposed to invasive procedures, was taking medications that may predispose to this type of infection, and was found to have a congenital immunodeficiency.
Infantile Pyknocytosis: An Uncommon Cause of Newborn Hemolytic Anemia
Authors: Castillo Jayme , Ness Tara E. , Mehta Parth S.
Published: April 2019

Infantile pyknocytosis is a rare cause of neonatal hemolytic anemia, which presents in the first few weeks of life. We report a classic case of infantile pyknocytosis that presented to our institution with rebound hyperbilirubinemia after receiving phototherapy. The infant was found to have a hemoglobin of 5.8 g/dL, requiring a total of 15 mL/kg of red blood cells (in 2 separate transfusions) before discharge. The diagnosis was ultimately made by a review of the peripheral blood smear. We review the literature and suggest pediatricians consider infantile pyknocytosis on their differential when hemolytic anemia presents in the newborn period.
Attosecond soft X-ray high harmonic generation
Authors: Johnson Allan S. , Avni Timur , Larsen Esben W. , Austin Dane R. , Marangos Jon P.
Published: April 2019

High harmonic generation (HHG) of an intense laser pulse is a highly nonlinear optical phenomenon that provides the only proven source of tabletop attosecond pulses, and it is the key technology in attosecond science. Recent developments in high-intensity infrared lasers have extended HHG beyond its traditional domain of the XUV spectral range (10–150 eV) into the soft X-ray regime (150 eV to 3 keV), allowing the compactness, stability and sub-femtosecond duration of HHG to be combined with the atomic site specificity and electronic/structural sensitivity of X-ray spectroscopy. HHG in the soft X-ray spectral region has significant differences from HHG in the XUV, which necessitate new approaches to generating and characterizing attosecond pulses. Here, we examine the challenges and opportunities of soft X-ray HHG, and we use simulations to examine the optimal generating conditions for the development of high-flux, attosecond-duration pulses in the soft X-ray spectral range.

This article is part of the theme issue ‘Measurement of ultrafast electronic and structural dynamics with X-rays’.
Imaging of transition charge densities involving carbon core excitations by all X-ray sum-frequency generation
Authors: Cho Daeheum , Rouxel Jérémy R. , Kowalewski Markus , Lee JinYong , Mukamel Shaul
Published: April 2019

X-ray diffraction signals from the time-evolving molecular charge density induced by selective core excitation of chemically inequivalent carbon atoms are calculated. A narrowband X-ray pulse selectively excites the carbon K-edge of the –CH
3
or –CH
2
F groups in fluoroethane (CH
3
–CH
2
F). Each excitation creates a distinct core coherence which depends on the character of the electronic transition. Direct propagation of the reduced single-electron density matrix, using real-time time-dependent density functional theory, provides the time-evolving charge density following interactions with external fields. The interplay between partially filled valence molecular orbitals upon core excitation induces characteristic femtosecond charge migration which depends on the core–valence coherence, and is monitored by the sum-frequency generation diffraction signal.

This article is part of the theme issue ‘Measurement of ultrafast electronic and structural dynamics with X-rays’.
Optical control, selection and analysis of population dynamics in ultrafast protein X-ray crystallography
Authors: Hutchison Christopher D. M. , van Thor Jasper J.
Published: April 2019

Ultrafast pump-probe X-ray crystallography has now been established at X-ray free electron lasers that operate at hard X-ray energies. We discuss the performance and development of current applications in terms of the available data quality and sensitivity to detect and analyse structural dynamics. A discussion of technical capabilities expected at future high repetition rate applications as well as future non-collinear multi-pulse schemes focuses on the possibility to advance the technique to the practical application of the X-ray crystallographic equivalent of an impulse time-domain Raman measurement of vibrational coherence. Furthermore, we present calculations of the magnitude of population differences and distributions prepared with ultrafast optical pumping of single crystals in the typical serial femtosecond crystallography geometry, which are developed for the general uniaxial and biaxial cases. The results present opportunities for polarization resolved anisotropic X-ray diffraction analysis of photochemical populations for the ultrafast time domain.

This article is part of the theme issue ‘Measurement of ultrafast electronic and structural dynamics with X-rays’.
On the limits of observing motion in time-resolved X-ray scattering
Authors: Ware Matthew R. , Glownia James M. , Natan Adi , Cryan James P. , Bucksbaum Philip H.
Published: April 2019

Limits on the ability of time-resolved X-ray scattering (TRXS) to observe harmonic motion of amplitude,
A
and frequency,
ω
0
, about an equilibrium position,
R
0
, are considered. Experimental results from a TRXS experiment at the LINAC Coherent Light Source are compared to classical and quantum theories that demonstrate a fundamental limitation on the ability to observe the amplitude of motion. These comparisons demonstrate dual limits on the spatial resolution through
Q
max
and the temporal resolution through
ω
max
for observing the amplitude of motion. In the limit where
ω
max
 ≈ 
ω
0
, the smallest observable amplitude of motion is
A
 = 2
π
/
Q
max
. In the limit where
ω
max
≥2
ω
0
,
A
≤2
π
/
Q
max
is observable provided there are sufficient statistics.

This article is part of the theme issue ‘Measurement of ultrafast electronic and structural dynamics with X-rays’.
Compounding the disturbance: Family forest owner reactions to invasive forest insects
Authors: Markowski-Lindsay Marla , Borsuk Mark E. , Butler Brett J. , Duveneck Matthew J. , Holt Jonathan , Kittredge David B. , Laflower Danelle , MacLean Meghan Graham , Orwig David , Thompson Jonathan R.
Published: March 2019

Invasive forest insect and pathogens (FIP) are having significant, direct, adverse impacts. Interactions between FIPs and forest owners have the potential to create ecosystem impacts that compound direct impacts. We assessed family forest owners’ responses to numerous contingent behavior, FIP-outbreak scenarios in the northeastern U.S. based on FIP outbreak attributes. Sixty-two percent of scenario responses (n=2,752) reflected a harvest intent as a result of FIPs; 84% of respondents (n=688) would consider harvesting in at least one of the four hypothetical scenarios presented to them. Harvest intention increased with greater FIP-related tree mortality and decreased with delayed total tree mortality. Owners with larger holdings, who had previously harvested forest products, and live on their forestland had greater intentions to harvest in response to FIPs. Results suggest that FIPs could transform the regional harvest regime with socio-ecological impacts that are distinct from those caused by FIPs or harvesting alone.
Oriented basement membrane fibrils provide a memory for F-actin planar polarization via the Dystrophin-Dystroglycan complex during tissue elongation
Authors: Campos Fabiana Cerqueira , Dennis Cynthia , Alégot Hervé , Fritsch Cornelia , Isabella Adam , Pouchin Pierre , Bardot Olivier , Horne-Badovinac Sally , Mirouse Vincent
Published: March 2019

How extracellular matrix participates to tissue morphogenesis is still an open question. In theDrosophilaovarian follicle, it has been proposed that after Fat2-dependent planar polarization of the follicle cell basal domain, oriented basement membrane (BM) fibrils and F-actin stress fibers constrain follicle growth, promoting its axial elongation. However, the relationship between BM fibrils and stress fibers and their respective impact on elongation are unclear. We found that Dystroglycan (Dg) and Dystrophin (Dys) are involved in BM fibril deposition. Moreover, they orient stress fibers, by acting locally and in parallel to Fat2. Nonetheless, Dg-Dys complex-mediated cell autonomous control of F-actin fibers orientation relies on the previous BM fibril deposition, indicating two distinct but interdependent functions. Thus, the Dg-Dys complex works as a critical organizer of the epithelial basal domain, regulating both F-actin and BM. Furthermore, BM fibrils act as a persistent cue for the orientation of stress fibers that are the main effector of elongation.
Controlling Heterogeneity and Increasing Titer from Riboswitch-RegulatedBacillus subtilisSpores for Time-Delayed Protein Expression Applications
Authors: Tamiev Denis , Lantz Alyssa , Vezeau Grace , Salis Howard , Reuel Nigel F.
Published: March 2019

Sporulated cells have potential as time-delayed expression chassis of proteins for applications such as ‘on-demand’ biologics production, whole cell biosensors, or oral vaccines. However, the desired attributes of high expression rates and low product variances are difficult to maintain from germinated spores. In this work we study the effect of an integratingvs.theta replicating plasmid in a wild-typeBacillus subtilisand two PolY mutants. The cells were engineered to produce a fluorescent reporter protein (RFP) under the control of a riboswitch activated by theophylline. This allowed for greater sensitivity to point mutations. The fluorescence and cell growth curves were fit with a custom kinetic model and a peak kinetic rate (LKPmax) was extracted for each clonal population (n = 30 for all cell, vector, and growth combinations). Plasmid based expression yields higher (8.7x) expression rates due to an increased copy number of the expression cassette (10x over integrated). The variance of LKPmaxvalues increased 2.07x after sporulation for the wild type strain. This increase in variance from sporulation is very similar to what is observed with UV exposure. This effect can be partially mitigated by the use of PolY knockouts observed in suspended cell growths and adherent biofilms.
A toolset of constitutive promoters for metabolic engineering ofRhodosporidium toruloides
Authors: Nora Luísa Czamanski , Wehrs Maren , Kim Joonhoon , Cheng Jan-Fang , Tarver Angela , Simmons Blake A. , Magnuson Jon , Harmon-Smith Miranda , Silva-Rocha Rafael , Gladden John M. , Mukhopadhyay Aindrila , Skerker Jeffrey M. , Kirby James
Published: March 2019

Background

Rhodosporidium toruloidesis a promising host for the production of bioproducts from lignocellulosic biomass. A key prerequisite for efficient pathway engineering is the availability of robust genetic tools and resources. However, there is a lack of characterized promoters to drive expression of heterologous genes for strain engineering inR. toruloides.

Results

Our data describes a set of nativeR. toruloidespromoters, characterized over time in four different media commonly used for cultivation of this yeast. The promoter sequences were selected using transcriptional analysis and several of them were found to drive expression bidirectionally. We measured promoter expression strength by flow cytometry using a dual fluorescent reporter system. From these analyses, we found a total of 20 constitutive promoters (12 monodirectional and 8 bidirectional) of potential value for genetic engineering ofR. toruloides.

Conclusions

We present a list of robust and constitutive, native promoters to facilitate genetic engineering ofR. toruloides.This set of thoroughly characterized promoters significantly expands the range of engineering tools available for this yeast and can be applied in future metabolic engineering studies.
Immortalization of different breast epithelial cell types results in distinct mitochondrial mutagenesis
Authors: Kwon Sujin , Kim Susan S. , Nebeck Howard E. , Ahn Eun Hyun
Published: March 2019

Different phenotypes of normal cells might influence genetic profiles, epigenetic profiles, and tumorigenicities of their transformed derivatives. In this study, we investigated whether the whole mitochondrial genome of immortalized cells can be attributed to different phenotypes (stem vs non-stem) of their normal epithelial cell originators. To accurately determine mutations, we employed Duplex Sequencing, which exhibits the lowest error rates among currently available DNA sequencing methods. Our results indicate that the vast majority of observed mutations of the whole mitochondrial DNA occur at low-frequency (rare mutations). The most prevalent rare mutation types are C→T/G→A and A→G/T→C transitions. Frequencies and spectra of homoplasmic point mutations are virtually identical between stem cell-derived immortalized (SV1) cells and non-stem cell-derived immortalized (SV22) cells, verifying that both cell types were derived from the same woman. However, frequencies of rare point mutations are significantly lower in SV1 cells (5.79×10-5) than in SV22 cells (1.16×10-4). Additionally, the predicted pathogenicity for rare mutations in the mitochondrial tRNA genes is significantly lower (by 2.5-fold) in SV1 cells than in SV22 cells. Our findings suggest that the immortalization of normal cells with stem cell features leads to decreased mitochondrial mutagenesis, particularly in noncoding RNA regions. The mutation spectra and mutations specific to stem cell-derived immortalized cells (vs non-stem cell derived) have implications in characterizing heterogeneity of tumors and understanding the role of mitochondrial mutations in immortalization and transformation of human cells.
Mitochondrial dynamics and mitophagy are necessary for proper invasive growth in Rice Blast
Authors: Kou Yanjun , He Yunlong , Qiu Jiehua , Yazhou Shu , Yang Fan , Deng YiZhen , Naqvi Naweed I.
Published: March 2019

Magnaporthe oryzaecauses Blast disease, which is one of the most devastating infections in rice and several important cereal crops.M. oryzaeneeds to coordinate gene regulation, morphological changes, nutrient acquisition, and host evasion, in order to invade and proliferate within the plant tissues. Thus far, the molecular mechanisms underlying the regulation of invasive growthin plantahave remained largely unknown. We identified a precise filamentous-punctate-filamentous cycle in mitochondrial morphology duringMagnaporthe-Rice interaction. Interestingly, loss of either the mitochondrial fusion (MoFzo1) or fission (MoDnm1) machinery, or inhibition of mitochondrial fission using Mdivi-1 caused significant reduction inM. oryzaepathogenicity. Furthermore, exogenous carbon source(s) but not antioxidant treatment delayed such mitochondrial dynamics/transition during invasive growth. Such nutrient-based regulation of organellar dynamics preceded MoAtg24-mediated mitophagy, which was found to be essential for proper biotrophic development and invasive growthin planta. We propose that precise mitochondrial dynamics and mitophagy occur during the transition from biotrophy to necrotrophy, and are required for proper induction and establishment of the blast disease in rice.
Ultrasound- and microbubble-mediated targeted delivery of therapeutic microRNA-loaded nanocarriers to deep liver and kidney tissues in pigs
Authors: Di Ianni Tommaso , Bose Rajendran J.C. , Sukumar Uday K. , Bachawal Sunitha , Wang Huaijun , Telichko Arsenii , Herickhoff Carl D. , Robinson Elise , Baker Sam , Vilches-Moure José G. , Felt Stephen A. , Gambhir Sanjiv S. , Paulmurugan Ramasamy , Dahl Jeremy D.
Published: March 2019

In this study, we designed and validated a platform for ultrasound (US) and microbubble (MB)-mediated delivery of FDA-approved pegylated poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) loaded with anticancer microRNAs (miRNAs) to deep tissues in a pig model. Small RNAs have the ability to reprogram tumor cells and sensitize them to clinically used chemotherapy. However, to overcome their short intravascular circulation half-life and achieve controlled and sustained release into tumor cells, anticancer miRNAs need to be encapsulated into NPs. Moreover, focused US combined with gas-filled MBs provides a safe and noninvasive way to improve the permeability of tumor vasculature and increase the delivery efficiency of drug-loaded nanocarriers. A single handheld, curvilinear US array was used in this study for image-guidance and therapy with clinical-grade SonoVue MBs. First, we validated the platform on phantoms to optimize the MB cavitation dose based on acoustic parameters, including peak negative pressure, pulse length, and pulse repetition frequency. We then tested the system in vivo by delivering PLGA-NPs co-loaded with antisense-miRNA-21 and antisense-miRNA-10b in pig liver and kidney. Enhanced miRNA delivery was observed (1.9- to 3.7-fold increase) as a result of the US-MB treatment compared to untreated control regions. Additionally, we used highly fluorescent semiconducting polymer nanoparticles (SPNs) co-delivered with miRNA-loaded PLGA-NPs to visually assess NP delivery. Fluorescent microscopy of SPNs confirmed NP extravasation and showed the presence of particles in the extravascular compartment. Hematoxylin and eosin staining of treated tissues did not reveal tissue damage. The results presented in this manuscript suggest that enhanced delivery of miRNA-loaded NPs to target regions in deep organs is feasible in large animal models using the proposed platform.
Single cell transcriptomics identifies master regulators of neurodegeneration in SOD1 ALS motor neurons
Authors: Namboori Seema C. , Thomas Patricia , Ames Ryan , Hawkins Sophie , Garrett Lawrence O. , Willis Craig R. G. , Rosa Alessandro , Stanton Lawrence W. , Bhinge Akshay
Published: March 2019

Background

Bulk RNA-Seq has been extensively utilized to investigate the molecular changes accompanying motor neuron degeneration in Amyotrophic Lateral Sclerosis (ALS). However, due to the heterogeneity and degenerating phenotype of the neurons, it has proved difficult to assign specific changes to neuronal subtypes and identify which factors drive these changes. Consequently, we have utilized single cell transcriptomics of degenerating motor neurons derived from ALS patients to uncover key transcriptional drivers of dysfunctional pathways.

Results

Single cell analysis of spinal neuronal cultures derived from SOD1 E100G ALS and isogenic iPSCs allowed us to classify cells into neural subtypes including motor neurons and interneurons. Differential expression analysis between disease and control motor neurons revealed downregulation of genes involved in synaptic structure, neuronal cytoskeleton, mitochondrial function and autophagy. Interestingly, interneurons did not show similar suppression of these homeostatic functions. Single cell expression data enabled us to derive a context-specific transcriptional network relevant to ALS neurons. Master regulator analysis based on this network identified core transcriptional factors driving the ALS MN gene dysregulation. Specifically, we identified activation of SMAD2, a downstream mediator of the TGF-β signalling pathway as a potential driving factor of ALS motor neuron degeneration. Our phenotypic analysis further confirmed that an activated TGF-β signalling is major driver of motor neuron loss in SOD1 ALS. Importantly, expression analysis of TGFβ target genes and computational analysis of publicly available datasets indicates that activation of TGFβ signalling may be a common mechanism shared between SOD1, FUS and sporadic ALS.

Conclusions

Our results demonstrate the utility of single cell transcriptomics in mapping disease-relevant gene regulatory networks driving neurodegeneration in ALS motor neurons. We find that ALS-associated mutant SOD1 targets transcriptional networks that perturb motor neuron homeostasis.
Multi-Trait Improvement by Predicting Genetic Correlations in Breeding Crosses
Authors: Neyhart Jeffrey L. , Lorenz Aaron J. , Smith Kevin P.
Published: March 2019

The many quantitative traits of interest to plant breeders are often genetically correlated, which can complicate progress from selection. Improving multiple traits may be enhanced by identifying parent combinations – an important breeding step – that will deliver more favorable genetic correlations (rG). Modeling the segregation of genomewide markers with estimated effects may be one method of predictingrGin a cross, but this approach remains untested. Our objectives were to: (i) use simulations to assess the accuracy of genomewide predictions ofrGand the long-term response to selection when selecting crosses on the basis of such predictions; and (ii) empirically measure the ability to predict genetic correlations using data from a barley (Hordeum vulgareL.) breeding program. Using simulations, we found that the accuracy to predictrGwas generally moderate and influenced by trait heritability, population size, and genetic correlation architecture (i.e. pleiotropy or linkage disequilibrium). Among 26 barley breeding populations, the empirical prediction accuracy ofrGwas low (−0.012) to moderate (0.42), depending on trait complexity. Within a simulated plant breeding program employing indirect selection, choosing crosses based on predictedrGincreased multi-trait genetic gain by 11-27% compared to selection on the predicted cross mean. Importantly, when the starting genetic correlation was negative, such cross selection mitigated or prevented an unfavorable response in the trait under indirect selection. Prioritizing crosses based on predicted genetic correlation can be a feasible and effective method of improving unfavorably correlated traits in breeding programs.
Urban ecology of arboviral mosquito vectors along the Kenyan coast
Authors: Karisa Jonathan , Muriu Simon , Omuoyo Donwilliams , Karia Boniface , Nyamwaya Doris , Rono Martin , Warimwe George , Mwangangi Joseph , Mbogo Charles
Published: March 2019

Background

The emergence and re-emergence of arboviral infections particularly Chikungunya, dengue hemorrhagic fever, rift valley fever, and yellow fever in humans around the world threatens global health and security. The purpose of this study was to determine the urban ecology of the common arboviral mosquito vectors in urban Coastal Kenya areas.

Materials and Methods

The current study was conducted in urban settings of Kilifi and Mombasa counties in coastal Kenya in 2016 to 2017. Adult mosquitoes were collected both indoors and outdoors by CDC light traps and BG-Sentinel traps respectively. All blood fed mosquitoes were tested for blood meal sources by an Enzyme Linked Immunosorbent Assay (ELISA). Mosquito larvae were collected using standard dippers and pipettes. Egg survivorship in dry soil was evaluated by collecting of soil samples from dry potential breeding habitats, watering them for hatching and rearing of the eventual larvae to adults. Mosquitoes were screened forFlavivirus, Alphavirus,andPhlebovirusarboviruses using Reverse Transcriptase quantitative Polymerase Chain Reaction (RT qPCR).

Results

A total of 3,264 adult mosquitoes belonging to ten species ofCulex, AedesandAnopheleswere collected. Overall, the predominant species wereCx. quinquefasciatus72.4% (n=2,364) andAe. aegypti,25.7%, (n=838). A total of 415 breeding habitat types were identified indoors (n=317) and outdoors (n=98). The most productive habitat types in both indoors and outdoors were: assorted small containers, water tanks, drainages, drums and jericans. Overall, 62% (n=18) of the soil samples collected from the two sites (Kilifi and Malindi) were positive for larvae which were used as proxy to measure the presence of eggs. The mosquitoes had high preference for human blood (29.81%) and chicken (3.73%) but none had fed on either goat or bovine. Of 259 mosquitoes tested for viral infection, 11.6% were positive forflavivirusonly.

Conclusion

Domestic and peri-domestic containers were identified to be the key breeding areas of arboviral vectors. Therefore, efforts should be put in place targeting the productive habitat types.
Chronic corticosterone administration induces negative valence and impairs positive valence behaviors in mice
Authors: Dieterich Andrew , Srivastava Prachi , Sharif Aitesam , Stech Karina , Samuels Benjamin A.
Published: March 2019

Behavioral approaches utilizing rodents to study mood disorders have focused primarily on negative valence behaviors associated with potential threat (anxiety). However, for disorders such as depression, positive valence behaviors that assess reward processing may be more translationally-valid and predictive of antidepressant treatment outcome. Chronic corticosterone (CORT) administration is a well-validated pharmacological stressor that increases negative valence behaviors (David et al., 2009; Gourley et al., 2008a,b; Gourley et al., 2012; Olausson et al., 2013). However, whether chronic stress paradigms such as CORT administration also lead to deficits in positive valence behaviors remains unclear. We treated male C57BL/6J mice with chronic CORT and assessed both negative and positive valence behaviors. We found that CORT induced negative valence behaviors associated with anxiety in the open field and NSF. Interestingly, CORT also impaired instrumental acquisition, reduced sensitivity to a devalued outcome, reduced breakpoint in progressive ratio, and impaired performance in probabilistic reversal learning. Taken together, these results demonstrate that chronic CORT administration at the same dosage both induces negative valence behaviors associated with anxiety and impairs positive valence behaviors associated with reward processing. These data suggest that CORT administration is a useful experimental system for preclinical approaches to studying stress-induced mood disorders.

Significance Statement

Chronic exposure to stress can precipitate mood disorders such as anxiety and depression. However, most studies focus on the effects of chronic stress on increasing negative affect behaviors. Elucidating how chronic stress impacts translationally-valid positive valence behaviors is less studied. Here, we show that chronic pharmacological stress induces negative affect behaviors associates with anxiety and impairs reward-related, positive valence behaviors in mice.
Analysis of 100 high-coverage genomes from a pedigreed captive baboon colony
Authors: Robinson Jacqueline A. , Belsare Saurabh , Birnbaum Shifra , Newman Deborah E. , Chan Jeannie , Glenn Jeremy P. , Ferguson Betsy , Cox Laura A. , Wall Jeffrey D.
Published: March 2019

Baboons (genus Papio) are broadly studied in the wild and in captivity. They are widely used as a nonhuman primate model for biomedical studies, and the Southwest National Primate Research Center (SNPRC) at Texas Biomedical Research Institute has maintained a large captive baboon colony for more than 50 yr. Unlike other model organisms, however, the genomic resources for baboons are severely lacking. This has hindered the progress of studies using baboons as a model for basic biology or human disease. Here, we describe a data set of 100 high-coverage whole-genome sequences obtained from the mixed colony of olive (P. anubis) and yellow (P. cynocephalus) baboons housed at the SNPRC. These data provide a comprehensive catalog of common genetic variation in baboons, as well as a fine-scale genetic map. We show how the data can be used to learn about ancestry and admixture and to correct errors in the colony records. Finally, we investigated the consequences of inbreeding within the SNPRC colony and found clear evidence for increased rates of infant mortality and increased homozygosity of putatively deleterious alleles in inbred individuals.
Optical performance and radiation stability of polymer X-ray refractive nano-lenses
Authors: Barannikov Alexander , Polikarpov Maxim , Ershov Petr , Bessonov Vladimir , Abrashitova Ksenia , Snigireva Irina , Yunkin Vyacheslav , Bourenkov Gleb , Schneider Thomas , Fedyanin Andrey A. , Snigirev Anatoly
Published: April 2019

Full-field X-ray imaging and microscopy with polymer compound refractive nano-lenses is demonstrated. Experiments were carried out at beamline ID13 at the European Synchrotron and yielded a resolution of 100 nm. The lenses were demonstrated to be functioning even after an absorbed dose of ∼107 Gy. This article also discusses issues related to lens aberrations, astigmatism and radiation stability, and thus ways of improving the lens further are considered. Polymer nano-lenses are versatile and are promissing for nano-focusing and compact X-ray microscopy.
Competition suppresses shrubs during early, but not late, stages of arid grassland–shrubland state transition
Authors: Pierce Nathan A. , Archer Steven R. , Bestelmeyer Brandon T.
Published: April 2019

Transitions from grass to woody plant dominance, widely reported in arid systems, are typically attributed to changes in disturbance regimes in combination with abiotic feedbacks, whereas biotic mechanisms such as competition and facilitation are often overlooked. Yet, research in semi‐arid and subhumid savannas indicates that biotic interactions are important drivers in systems at risk for state transition. We sought to bridge this divide by experimentally manipulating grass‐on‐shrub and shrub‐on‐shrub interactions in early and late stages of grassland–shrubland state transition, respectively, and to assess the extent to which these interactions might influence arid land state transition dynamics.

Target Prosopis glandulosa shrubs had surrounding grasses or conspecific neighbours left intact or killed with foliar herbicide, and metrics of plant performance were monitored over multiple years for shrubs with and without grass or shrub neighbours.

Productivity of small shrubs was enhanced by grass removal in years with above‐average precipitation, a result not evident in larger shrubs or during dry years. Proxy evidence based on nearest neighbour metrics suggested shrub–shrub competition was at play, but our experimental manipulations revealed no such influence.

Competition from grasses appears to attenuate the rate at which shrubs achieve the size necessary to modify the physical environment in self‐reinforcing ways, but only during the early stages of shrub encroachment. Our results further suggest that at late stages of grassland‐to‐shrubland state transitions, shrub–shrub competition will not slow the rate of shrub expansion, and suggest that maximum shrub cover is regulated by something other than density‐dependent mechanisms. We conclude that grass effects on shrubs should be included in assessments of desert grassland state transition probabilities and rates, and that desertification models in arid ecosystems that traditionally focus on disturbance and abiotic feedbacks should be broadened to incorporate spatial and temporal variations in competitive effects.

A plain language summary is available for this article.
Microbial diversity of an Antarctic subglacial community and high‐resolution replicate sampling inform hydrological connectivity in a polar desert
Authors: Campen Richard , Kowalski Julia , Lyons W. Berry , Tulaczyk Slawek , Dachwald Bernd , Pettit Erin , Welch Kathleen A. , Mikucki Jill A.
Published: March 2019

Antarctic subglacial environments host microbial ecosystems and are proving to be geochemically and biologically diverse. The Taylor Glacier, Antarctica, periodically expels iron‐rich brine through a conduit sourced from a deep subglacial aquifer, creating a dramatic red surface feature known as Blood Falls. We used Illumina MiSeq sequencing to describe the core microbiome of this subglacial brine and identified previously undetected but abundant groups including the candidate bacterial phylum Atribacteria and archaeal phylum Pacearchaeota. Our work represents the first microbial characterization of samples collected from within a glacier using a melt probe, and the only Antarctic subglacial aquatic environment that, to date, has been sampled twice. A comparative analysis showed the brine community to be stable at the operational taxonomic unit level of 99% identity over a decade. Higher resolution sequencing enabled deconvolution of the microbiome of subglacial brine from mixtures of materials collected at the glacier surface. Diversity patterns between this brine and samples from the surrounding landscape provide insight into the hydrological connectivity of subglacial fluids to the surface polar desert environment. Understanding subice brines collected on the surfaces of thick ice covers has implications for analyses of expelled materials that may be sampled on icy extraterrestrial worlds.
Why Human Rights Matter for Our Future: The Views of Three Young People
Authors: Smith Jude , Richard Khalil , Siguake Natasha ,   and the charity ‘sheffield futures’
Published: March 2019

This article consists of statements by three young people with a passion for human rights. Two of the young people, Jude Smith (aged thirteen) and Khalil Richard (aged twenty) are members of the Sheffield Youth Cabinet. The third young person, Natasha Siguake (aged twenty), is a Young Advisor for Sheffield Futures. The three contributors talk about the human rights that are most important to them and why human rights are important for the future.
Encouraging Knowledge Transfer in Food Science and Nutrition Education: Suggestions from Cognitive Research
Authors: Sumeracki Megan A. , Weinstein-Jones Yana , Nebel Cynthia L. , Schmidt Shelly J.
Published: March 2019

For several decades, cognitive psychologists have been studying how we learn, and from this work it becomes possible to identify ways to help students learn in the classroom effectively. Importantly, this work does not just inform how to memorize facts, but also how to learn complex material in a way that allows students to apply what they are learning in future situations. The laboratory to classroom model used by many researchers to apply cognitive psychology to real educational situations, such as classroom learning and students’ independent studying, is described first. Then the focus turns to important issues within education, such as students’ ability to transfer knowledge to new situations and understand complex material. Finally, three learning strategies are discussed (concrete examples, elaborative interrogation, and retrieval practice) that instructors can implement to help students to both acquire knowledge and apply it to new situations, integrating examples from food science and nutrition.
Proceedings of the Inaugural Strategy Meeting for the Establishment of a Southeast Asia Regional Therapeutic Plasma Exchange Consortium for Neurological Disorders
Authors: Viswanathan Shanthi , Appiwatanakul Metha , Nayak Ashwini , Islam Badrul , Khatri Bhupendra , Pangeran David , Bambardekar Himanshu , Maharani Kartika , Tan Kevin , Alexander Mathew , Hussain Mohammad E , Adenan Mohd S , Danapaul Nabil AA , Khalife Najib , Ohnmar Ohnmar , Ong Beng Hooi , Estiasari Riwanti , Hanifa Sari N , Siritho Sasitorn , Ng Chen Fei , Ratna Sylvanie , Umapathi Thirugnanam , Thit Win M , Ramli Yetty , Lee Yvonne YL , Hiew Fu Liong
Published: March 2019

In conjunction with the third regional Southeast Asian (SEA) therapeutic plasma exchange (TPE) conference in Kuala Lumpur, Malaysia, 25 clinicians and researchers from SEA and South Asian countries attended the inaugural strategy meeting for the establishment of a regional TPE consortium for neurological disorders. The primary objective was to establish regional collaboration to improve delivery of TPE services in SEA. A pre‐meeting survey was conducted to gather insights on disease spectrum, contextual practice challenges, and the need for a regional TPE consensus. Challenges identified include limited healthcare funding in support of diagnostic workup, TPE therapy, as well as development of clinical infrastructure and expertise capacity building. There was favorable interest in developing a working plan contextualized to this region. Strategies to overcome challenges were discussed. This included the need for a comprehensive referral system and network of regional TPE centers suited to local needs, supported by innovative TPE delivery programs.
Long‐term efficacy and safety of vedolizumab in patients with inflammatory bowel diseases: A real‐life experience from a tertiary referral center
Authors: Dragoni Gabriele , Bagnoli Siro , Le Grazie Marco , Campani Claudia , Rogai Francesca , Manetti Natalia , Bensi Carolina , Macrì Giuseppe , Galli Andrea , Milla Monica
Published: March 2019

Objective

The study aimed to evaluate the long‐term efficacy and safety of vedolizumab in a real‐life cohort of patients with inflammatory bowel diseases enrolled at a tertiary referral center.

Methods

Data were retrospectively collected from August 2016 to November 2018. The primary outcomes were clinical response and remission at 14, 24, and 52 weeks, and steroid‐free remission rate (SFRR) at 52 weeks. Endoscopic response and remission rates at 52 weeks were the secondary outcomes.

Results

Altogether 49 patients (22 with ulcerating colitis [UC] and 27 with Crohn’s Disease [CD]) were enrolled. The clinical response rate gradually dropped from 85% and 50% in CD and UC, respectively, at week 14 to 59% and 25% at week 52, with significantly a higher response in CD at week 14. The endoscopic response at week 52 was 55% in CD and 25% in UC (P = 0.21). CD group had a higher SFRR than UC group (41% vs 20%) at 52 weeks, although the difference was not statistically significant. Similar clinical and endoscopic rates were observed in biologic‐naive and ‐experienced patients. We reported no discontinuation due to adverse drug reactions, and only mild to moderate events.

Conclusions

In our cohort the clinical response in the induction phase was similar to those of registered trials, despite surprising better results for CD. During the maintenance phase we observed an higher drop out than in the reported literatures. Of note, its good safety profile makes vedolizumab a reliable choice in patients with contraindications to anti‐tumor necrosis factor agents.
Spatial analysis of a hydrocarbon waste‐remediating landfarm demonstrates influence of management practices on bacterial and fungal community structure
Authors: Bergsveinson Jordyn , Perry Benjamin J. , Simpson Gavin L. , Yost Christopher K. , Schutzman Robert J. , Hall Britt D. , Cameron Andrew D. S.
Published: March 2019

Cultivation of dedicated soil plots called ‘landfarms' is an effective technology for bioremediation of hydrocarbon waste generated by various industrial practices. To understand the influence of soil conditions on landfarm microbial communities, analysis of bacterial and fungal community structure using next‐generation sequencing at different sections and depths was performed across a hydrocarbon‐waste landfarm in Regina, Saskatchewan, Canada. While a core set of hydrocarbon‐associated bacterial and fungal taxa are present throughout the landfarm, unique bacterial and fungal operational taxonomic units are differentially abundant at sections within the landfarm, which correlate with differences in soil physiochemical properties and management practices. Increased frequency of waste application resulted in strong positive correlations between bacterial community assemblages and elevated amounts of oil, grease and F3 – F4 hydrocarbon fractions. In areas of standing water and lower application of hydrocarbon, microbial community structure correlated with soil pH, trace nutrients and metals. Overall, diversity and structure of bacterial communities remain relatively stable across the landfarm, while in contrast, fungal community structure appears more responsive to soil oxygen conditions. Results are consistent with the hypothesis that years of bioremediation activity have shaped microbial communities; however, several management practices can be undertaken to increase efficiency of remediation, including the removal of standing water and soil tilling across the landfarm.
PCSK9 is Increased in Cerebrospinal Fluid of Individuals With Alcohol Use Disorder
Authors: Lee Ji Soo , Rosoff Daniel , Luo Audrey , Longley Martha , Phillips Monte , Charlet Katrin , Muench Christine , Jung Jeesun , Lohoff Falk W.
Published: April 2019

Background

Recent studies have shown that alcohol use affects the regulation and expression of proprotein convertase subtilisin/kexin 9 (PCSK9). While a major role of PCSK9 in hepatic function and lipid regulation has been clearly established, other pleiotropic effects remain poorly understood. Existing research suggests a positive association between PCSK9 expression in the brain and psychopathology, with increased levels of PCSK9 in the cerebrospinal fluid (CSF) of individuals with dementia and epigenetic modifications of PCSK9 associated with alcohol use disorder (AUD). In this study, we hypothesized that chronic alcohol use would increase PCSK9 expression in CSF.

Methods

PCSK9 levels in CSF were measured in individuals with AUD (n = 42) admitted to an inpatient rehabilitation program and controls (n = 25). CSF samples in AUD were assessed at 2 time points, at day 5 and day 21 after admission. Furthermore, plasma samples were collected and measured from the individuals with AUD.

Results

PCSK9 in CSF was significantly increased in the AUD group at day 5 and day 21 compared to the controls (p < 0.0001). Plasma PCSK9 levels were correlated positively with CSF PCSK9 levels in AUD (p = 0.0493).

Conclusions

Our data suggest that PCSK9 is elevated in the CSF of individuals with AUD, which may indicate a potential role of PCSK9 in AUD. Additional studies are necessary to further elucidate the functions of PCSK9 in the brain.
The effects of sustained virological response to direct‐acting anti‐viral therapy on the risk of extrahepatic manifestations of hepatitis C infection
Authors: El‐Serag Hashem B. , Christie Israel C. , Puenpatom Amy , Castillo Diana , Kanwal Fasiha , Kramer Jennifer R.
Published: April 2019

Background

Direct‐acting anti‐viral (DAA) therapy may have a beneficial role in extrahepatic manifestations of hepatitis C virus (HCV) infection. However, the available data are limited.

Aim

To examine the effects of DAA treatment on the risk of several extrahepatic manifestations of HCV.

Methods

We conducted a retrospective cohort study of patients from the US Department of Veterans Affairs Corporate Data Warehouse who had a positive HCV RNA test and received first course of DAAs between 2012 and 2016. We calculated incidence rates by sustained virological response (SVR) status for six extrahepatic manifestations, and effect of SVR on these conditions was evaluated in adjusted Cox regression models.

Results

Of the 45 260 patients treated with DAA with mean follow‐up of 2.01 years, 41 711 (92.2%) experienced SVR. Incidence rates ranged from 0.17/1000 PY for porphyria cutanea tarda to 21.04/1000 PY for diabetes in the SVR group and 0.51/1000 PY for porphyria cutanea tarda to 23.11/1000 PY for diabetes in the no SVR group. The risk was reduced with SVR for mixed cryoglobulinaemia (adjusted HR (aHR) = 0.23; 95% CI 0.10‐0.56), glomerulonephritis (aHR = 0.61; 95% CI 0.41‐0.90) and lichen planus (aHR = 0.46; 95% CI 0.30‐0.70), but not for non‐Hodgkin's lymphoma (aHR = 0.86; 95% CI 0.52‐1.43) or diabetes (aHR = 0.98; 95% CI 0.81‐1.19). Non significant risk reduction was seen for porphyria cutanea tarda (aHR = 0.33; 95% CI 0.11‐1.03).

Conclusions

Successful DAA treatment resulting in SVR was associated with significant reductions in the risk of mixed cryoglobulinaemia, glomerulonephritis, lichen planus and possibly porphyria cutanea tarda, but not non‐Hodgkin's lymphoma or diabetes.
Trends in utilization and dosing of antipsychotic drugs in Scandinavia: Comparison of 2006 and 2016
Authors: Højlund Mikkel , Pottegård Anton , Johnsen Erik , Kroken Rune A. , Reutfors Johan , Munk‐Jørgensen Povl , Correll Christoph U.
Published: March 2019

Aims

The aim of this study was to investigate time trends in dosing and prevalence of antipsychotic prescriptions in Scandinavia.

Methods

We retrieved data on antipsychotic use between 2006 and 2016 from Danish, Norwegian and Swedish national prescription registers. For each antipsychotic, we calculated prevalence of use and mean doses, overall and for specific age groups (young, adults and elderly).

Results

Antipsychotic use in Scandinavia increased from 16.5 to 17.2 users/1000 inhabitants between 2006 and 2016 (+2.4%, annual change: 0.07 users/1000 inhabitants/year, 95% CI: 0.02–0.20, P = 0.02). In 2006, chlorprothixene and levomepromazine were the most commonly used antipsychotics. By 2016, quetiapine was the most used antipsychotic in all three countries and across all age groups, with an overall 1‐year prevalence of 4.05–9.97 users/1000 inhabitants (annual change: 0.57 users/1000 inhabitants/year, 95% CI: 0.54–0.60, P < 0.001). Quetiapine showed a marked decrease in mean doses during the 11‐year study period (0.46–0.28 defined daily doses (DDD)/user/day: 39.1%, −0.02 DDD/user/day/year, 95% CI: −0.020 to −0.015, P < 0.001). In 2016, the highest mean doses were seen for clozapine (0.90–1.07 DDD/user/day) and olanzapine (0.66–0.88 DDD/user/day).

Conclusions

There is an increased prevalence of antipsychotic prescriptions that coincides with low and/or decreasing mean doses of the majority of commonly used antipsychotics in Scandinavia. Of all antipsychotics, this development was most pronounced for quetiapine. Reasons for and consequences of increased antipsychotic use that lasts shorter periods of time requires further study.