bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differences between experienced and recalled breathlessness: a review
Authors: Sandberg Jacob , Ekström Magnus 
Published: July 2019

Purpose of review
Experienced breathlessness and recalled breathlessness are two different entities, which may be associated with different factors and might have different impacts on function for the individual. The aim was to review the knowledge from the last 2 years concerning experienced breathlessness and recalled breathlessness and related factors.

Recent findings
Experienced breathlessness was most often induced or measured during exercise testing in a lab environment using a modified Borg scale. It was associated with both psychological factors, such as social rejection, presence of others, psychosocial stress and prenatal exposure to stress, as well as physical factors, such as hypoxia and frequent exacerbations.
Recalled breathlessness was most often measured in epidemiological studies, most commonly using the modified Medical Research Council scale. It was associated with lung volumes, overweight, exercise training, frailty, smoking, personality traits, behavior and marital and occupational status.

Summary
No studies during the review period had directly compared experienced breathlessness and recalled breathlessness. Several factors were related to either experienced breathlessness or recalled breathlessness but no clear differences between factors were found in this review. There is a need for comparative studies using the same measurement methods and in the same settings in order to examine their relation.
Population genomics and pathotypic evaluation of the bacterial leaf blight pathogen of rice reveals rapid evolutionary dynamics of a plant pathogen
Authors: Zheng Jinshui , Song Zhiwei , Zheng Dehong , Hu Huifeng , Liu Hongxia , Zhao Yancun , Sun Ming , Ruan Lifang , Liu Fengquan 
Published: July 2019

AbstractXanthomonas oryzaepv.oryzae(Xoo) causes bacterial blight disease, which reduces crop yield by up to 50% in rice production. Despite its substantial threat on food production worldwide, knowledge about its population structure, virulence diversity and the relationship between them is limited. We used whole-genome sequencing to explore the diversity and evolution ofXooduring the past 30 years in the main rice-planting areas of China. Six separate lineages were revealed by phylogenomic analysis, with CX-5 and CX-6 predominating in the population for decades. The recent sporadic outbreaks were respectively caused byXooderived from these lineages especially the two major ones. The lineage and sub-lineage distribution of isolates strongly correlated to their geographical origin, which was found to be mainly determined by the planting of the two major rice subspecies,indicaandjaponica. Large-scale virulence testing was conducted to evaluate the diversity of pathogenicity forXoo.We found rapid virulence dynamics against rice, and its determinant factors including genetic background ofXoo, rice resistance genes and the planting environment of rice. Genetic background was investigated deeply by comparative genomics, which indicates that transposition events contributing the most to evolution of theXoogenome and the rapid diversification of virulence. This study provided a good model to understand the evolution and dynamics of plant pathogens in the context of interaction with their hosts which are influenced by both geographical conditions and farming practices.
Quantitative intravital imaging ofPlasmodium falciparumsporozoites: A novel platform to test malaria intervention strategies
Authors: Hopp Christine S. , Kanatani Sachie , Archer Nathan K. , Miller Robert J. , Liu Haiyun , Chiou Kevin , Miller Lloyd S. , Sinnis Photini 
Published: July 2019

AbstractMalaria infection starts with the injection of motilePlasmodiumsporozoites into the host’s skin during a mosquito bite. Previous studies using the rodent malaria model indicate that the dermal inoculation site may be where sporozoites are most vulnerable to antibodies, yet, functionalin vivoassays with human malaria parasites are lacking. Here, we present the first characterization ofP. falciparumsporozoites in the skin, comparing their motility to two rodent malaria species and investigating whether the environment of its natural host influencesP. falciparumsporozoite motility using a human skin xenograft model. The combined data suggest that in contrast to the liver and blood stages, the skin is not a species-specific barrier forPlasmodium. We observe thatP. falciparumsporozoites inoculated into mouse skin move with similar speed, displacement and duration, and enter blood vessels in similar numbers as the rodent parasites. Thus, interventions targetingP. falciparumsporozoite migration can be tested in the murine dermis. Importantly, to streamline quantification of sporozoite motility, we developed a toolbox allowing for automated detection and tracking of sporozoites in intravital microscopy videos. This establishes a platform to test vaccine candidates, immunization protocols, monoclonal antibodies and drug candidates for their impact on human malaria sporozoitesin vivo. Screening of intervention strategies forin vivoefficacy againstPfsporozoites using this new platform will have the potential to validate targets prior to expensive clinical trials.
The polyphagous plant pathogenic fungusBotrytis cinereaencompasses host-specialized and generalist populations
Authors: Mercier Alex , Carpentier Florence , Duplaix Clémentine , Auger Annie , Pradier Jean-Marc , Viaud Muriel , Gladieux Pierre , Walker Anne-Sophie 
Published: July 2019

AbstractThe host plant is often the main variable explaining population structure in fungal plant pathogens, because specialization contributes to reduce gene flow between populations associated with different hosts. Previous population genetic analysis revealed that French populations of the grey mould pathogenBotrytis cinereawere structured by hosts tomato and grapevine, suggesting host specialization in this highly polyphagous pathogen. However, these findings raised questions about the magnitude of this specialization and the possibility of specialization to other hosts. Here we report specialization ofB. cinereapopulations to tomato and grapevine hosts but not to other tested plants. Population genetic analysis revealed two pathogen clusters associated with tomato and grapevine, while the other clusters co-occurred on hydrangea, strawberry and bramble. Measurements of quantitative pathogenicity were consistent with host specialization of populations found on tomato, and to a lesser extent, populations found on grapevine. Pathogen populations from hydrangea and strawberry appeared to be generalist, while populations from bramble may be weakly specialized. Our results suggest that the polyphagousB. cinereais more accurately described as a collection of generalist and specialist individuals in populations. This work opens new perspectives for grey mold management, while suggesting spatial optimization of crop organization within agricultural landscapes.
Two-photon Imaging with Silicon Photomultipliers
Authors: Modi Mehrab , Turner Glenn C , Podgorski Kaspar 
Published: July 2019

AbstractSilicon photomultipliers (SiPMs) are a class of inexpensive and robust single-pixel detectors with applications similar to photomultiplier tubes (PMTs). We performed side-by-side comparisons of recently-developed SiPMs and a GaAsP PMT for two-photon fluorescence imaging of neural activity. Despite higher dark counts, which limit their performance at low photon rates (<1μs), SiPMs matched the signal-to-noise ratio of the GaAsP PMT at photon rates encountered in typical calcium imaging experiments due to their much lower pulse height variability. At higher photon rates and dynamic ranges encountered during high-speed two-photon voltage imaging, SiPMs significantly outperformed the GaAsP PMT.
Perturbation-based mapping of natural frequencies with direct intracranial stimulation of the human brain
Authors: Amengual Julià L , Stengel Chloé , Moreau Tristan , Adam Claude , Chavez Mario , Valero-Cabré Antoni 
Published: July 2019

ABSTRACTTheoretical and experimental evidence suggest that the induction of oscillatory activity by an external rhythmic source on a specific brain area is maximally efficient if the input pattern matches its so-called ‘natural’ frequency, defined as the predominant neural rhythm at which the activity of this area tends to fluctuate spontaneously. Based on this principle, single pulse Transcranial Magnetic Stimulation (TMS) coupled to scalp electroencephalography (EEG) has provided evidence of frequency-specific power increases within a unique ‘natural’ frequency band, considered common to the whole lobe.In an attempt to gain deeper insight into this phenomenon and set the basis for a finer-grained atlas of ‘natural’ frequencies, here we analyzed intracranial EEG (iEEG) signals modulated by single pulses of direct electrical brain stimulation in human patients implanted with depth multielectrodes. Our analyses revealed changes in local EEG activity emerging from local oscillators and contributing to a complex distribution of frequency-specific ‘natural’ rhythmic responses throughout cortical regions. Moreover, challenging the notion of ‘natural’ oscillations featuring a predominant frequency band characteristic for an entire lobe, our data support a rich diversity of spectral fingerprints (narrowband, vs. broadband or multiband) with single or multiple frequency peaks, often encompassing contiguous frequency bands, operating at a very local scale.Our findings contribute novel insights on which specific brain areas could be more likely to be synchronized at a given frequencies band and their preferred coupling frequencies, features that could ultimately inform on their structural and functional organization. Our results may also increase our mechanistic understanding of invasive and noninvasive brain stimulation and promote further developments of these approaches for the manipulation of brain oscillations subtending normal and impaired cognition.
Combined single-cell and spatial transcriptomics reveals the molecular, cellular and spatial bone marrow niche organization
Authors: Baccin Chiara , Al-Sabah Jude , Velten Lars , Helbling Patrick M. , Grünschläger Florian , Hernández-Malmierca Pablo , Nombela-Arrieta César , Steinmetz Lars M. , Trumpp Andreas , Haas Simon 
Published: July 2019

SUMMARYThe bone marrow (BM) constitutes the primary site for life-long blood production and skeletal regeneration. However, its cellular composition and the spatial organization into distinct ‘niches’ remains controversial. Here, we combine single-cell and spatially resolved transcriptomics to systematically map the molecular and cellular composition of the endosteal, sinusoidal, and arteriolar BM niches. This allowed us to transcriptionally profile all major BM resident cell types, determine their localization, and clarify the cellular and spatial sources of key growth factors and cytokines. Our data demonstrate that previously unrecognized Cxcl12-abundant reticular (CAR) cell subsets (i.e. Adipo- and Osteo-CAR cells) differentially localize to sinusoidal or arteriolar surfaces, locally act as ‘professional cytokine secreting cells’, and thereby establish distinct peri-vascular micro-niches. Importantly, we also demonstrate that the 3-dimensional organization of the BM can be accurately inferred from single-cell gene expression data using the newly developed RNA-Magnet algorithm. Together, our study reveals the cellular and spatial organization of BM niches, and offers a novel strategy to dissect the complex organization of whole organs in a systematic manner.One Sentence SummaryIntegration of single-cell and spatial transcriptomics reveals the molecular, cellular and spatial organization of bone marrow niches
A novel mosaic tetracycline resistance gene tet(S/M) detected in a multidrug-resistant pneumococcal CC230 lineage that underwent capsular switching in South Africa
Authors: Lo Stephanie W. , Gladstone Rebecca A. , van Tonder Andries J. , du Plessis Mignon , Cornick Jennifer E. , Hawkins Paulina A. , Madhi Shabir A. , Nzenze Susan A. , Kandasamy Rama , Ravikumar KL , Elmdaghri Naima , Kwambana-Adams Brenda , Grassi Almeida Samanta Cristine , Skoczynska Anna , Egorova Ekaterina , Titov Leonid , Saha Samir K. , Paragi Metka , Everett Dean B. , Antonio Martin , Klugman Keith P. , Li Yuan , Metcalf Benjamin J , Beall Bernard , McGee Lesley , Breiman Robert F. , Bentley Stephen D. , von Gottberg Anne ,   on behalf of The Global Pneumococcal Sequencing Consortium
Published: July 2019

SynopsisObjectiveWe reported a novel tetracycline-resistant gene in Streptococcus pneumoniae and investigated its temporal spread in relation to nationwide clinical interventions.MethodsWe whole genome sequenced 12,254 pneumococcal isolates from twenty-nine countries on an Illumina HiSeq Sequencer. Serotypes, sequence types and antibiotic resistance were inferred from genomes. Phylogeny was built based on single-nucleotide variants. Temporal changes of spread were reconstructed using a birth-death model.ResultsWe identified tet(S/M) in 131 pneumococcal isolates, 97 (74%) caused invasive pneumococcal diseases among young children (59% HIV-positive, where HIV status was available) in South Africa. A majority of tet(S/M)-positive isolates (129/131) belong to clonal complex (CC)230. A global phylogeny of CC230 (n=389) revealed that tet(S/M)-positive isolates formed a sub-lineage that exhibited multidrug-resistance. Using the genomic data and a birth-death model, we detected an unrecognised outbreak of this sub-lineage in South Africa between 2000 and 2004 with an expected secondary infections (R) of ~2.5. R declined to ~1.0 in 2005 and <1.0 in 2012. The declining epidemic coincided and could be related to the nationwide implementation of anti-retroviral treatment (ART) for HIV-infected individuals in 2004 and PCVs in late 2000s. Capsular switching from vaccine serotype 14 to non-vaccine serotype 23A was observed within the sub-lineage.ConclusionsThe prevalence of tet(S/M) in pneumococci was low and its dissemination was due to an unrecognised outbreak of CC230 in South Africa prior to ART and PCVs. However, capsular switching in this multidrug-resistant sub-lineage highlighted its potential to continue to cause disease in the post-PCV13 era.
Positive allosteric modulation of metabotropic glutamate receptor 5 modulates Akt and GSK3β signaling in vivo
Authors: Johnson Kari A. , Conn P. Jeffrey 
Published: July 2019

AbstractBackgroundPositive allosteric modulators (PAMs) of metabotropic glutamate receptor 5 (mGlu5) have behavioral effects predictive of antipsychotic activity in experimental models such as amphetamine-induced hyperlocomotion (AHL). However, the signaling mechanisms that contribute to the antipsychotic-like properties of mGlu5 PAMs are not well understood.MethodsBecause the Akt/GSK3β pathway has been implicated in schizophrenia and is modulated by known antipsychotic drugs, we evaluated the effects of systemic administration of two mGlu5 PAMs on Akt and GSK3β signaling using western blot analysis in both naïve and amphetamine-treated adult male rats.ResultsIn the dorsal striatum, the mGlu5-selective PAM VU0092273 (30 mg/kg) significantly increased Akt phosphorylation at residues associated with enhanced kinase activity, Thr308 and Ser473. Inhibitory phosphorylation of GSK3β at Ser9 was also increased. Similar effects were observed with a second mGlu5 PAM, VU0360172 (56.6 mg/kg). VU0092273 increased Akt phosphorylation levels in amphetamine-treated rats. Effects on Akt/GSK3β signaling were not limited to the striatum, as VU0092273 also increased Akt/GSK3β phosphorylation in the medial prefrontal cortex.ConclusionsThese findings suggest that mGlu5 PAMs that have antipsychotic-like efficacy in rats affect signaling pathways that are modulated by known antipsychotics, and raise the possibility that inhibition of GSK3β might contribute to the antipsychotic-like effects of mGlu5 PAMs.
MultIscale MultiObjective Systems Analysis (MIMOSA): an advanced metabolic modeling framework for complex systems
Authors: Gardner Joseph J. , Hodge Bri-Mathias S. , Boyle Nanette R. 
Published: July 2019

ABSTRACTIn natural environments, cells live in complex communities and experience a high degree of heterogeneity internally and in the environment. Unfortunately, most of the metabolic modeling approaches that are currently used assume ideal conditions and that each cell is identical, limiting their application to pure cultures in well-mixed vessels. Here we describe our development of MultIscale MultiObjective Systems Analysis (MIMOSA), a metabolic modeling approach that can track individual cells in both space and time, track the diffusion of nutrients and light and the interaction of cells with each other and the environment. As a proof-of concept study, we used MIMOSA to model the growth ofTrichodesmium erythraeum, a filamentous diazotrophic cyanobacterium which has cells with two distinct metabolic modes. The use of MIMOSA significantly improves our ability to predictively model metabolic changes and phenotype in more complex cell cultures.
The localization of chitin synthase mediates the patterned deposition of chitin in developing Drosophila bristles
Authors: Adler Paul N. 
Published: July 2019

AbstractThe insect exoskeleton is a complex structure that is a key for the life style of this very successful group of animals. It contains proteins, lipids and the N-acetyl glucosamine polymer chitin. Chitin is synthesized by the enzyme chitin synthase. In most body regions, chitin fibrils are found in a stack of parallel arrays that can be detected by transmission electron microscopy. Each array is rotated with respect to the layers above and below. In sensory bristles, chitin primarily accumulates in bands parallel to the proximal/distal axis of the bristle. These bands are visible by confocal microscopy providing experimental advantages. We have used this cell type and an edited chitin synthase gene to establish that the bands of chitin are closely associated with stripes of chitin synthase, arguing the localization of chitin synthase plays an important role in mediating the patterned deposition of chitin. This is reminiscent of what has been seen for chitin and chitin synthase in fungi and between cellulose and cellulose synthase in plants. Several genes are known to be essential for proper chitin deposition. We found one of these,Rab11is required for the insertion of chitin synthase into the plasma membrane and a second,duskylikeis required for plasma membrane chitin synthase to localize properly into stripes. We also established that the actin cytoskeleton is required for the proper localization of chitin synthase and chitin in developing sensory bristles.
A genome-wide CRISPR screen identifies ZCCHC14 as a host factor required for hepatitis B surface antigen production
Authors: Hyrina Anastasia , Jones Christopher , Chen Darlene , Clarkson Scott , Cochran Nadire , Feucht Paul , Hoffman Gregory , Lindeman Alicia , Russ Carsten , Sigoillot Frederic , Uehara Kyoko , Xie Lili , Ganem Don , Holdorf Meghan 
Published: July 2019

GRAPHICAL ABSTRACTSUMMARYA hallmark of chronic hepatitis B virus (CHB) infection is the presence of high circulating levels of non-infectious small lipid HBV surface antigen (HBsAg) vesicles. Although rare, sustained HBsAg loss is the idealized endpoint of any CHB therapy. A novel small molecule RG7834 has been previously reported to inhibit HBsAg expression by targeting terminal nucleotidyltransferase protein 4A and 4B (TENT4A and TENT4B). In this study, we describe a genome-wide CRISPR screen to identify other potential novel host factors required for HBsAg expression and to gain further insights into the mechanism of RG7834. We report more than 60 genes involved in regulating HBsAg and identified novel factors involved in RG7834 activity, including a zinc finger CCHC-type containing 14 (ZCCHC14) protein. We show that ZCCHC14, together with TENT4A/B, stabilizes HBsAg expression through HBV RNA tailing, providing a potential new therapeutic target to achieve functional cure in CHB patients.
Automated Cytogenetic Biodosimetry at Population-Scale
Authors: Rogan PK , Lu R , Mucaki E , Ali S , Shirley B , Li Y , Wilkins R , Norton F , Sevriukova O , Pham D , Ainsbury E , Moquat J , Cooke R , Peerlaproulx T , Waller E , Knoll JHM 
Published: July 2019

AbstractIntroductionThe dicentric chromosome (DC) assay accurately quantifies exposure to radiation, however manual and semi-automated assignment of DCs has limited its use for a potential large-scale radiation incident. The Automated Dicentric Chromosome Identifier and Dose Estimator Chromosome (ADCI) software automates unattended DC detection and determines radiation exposures, fulfilling IAEA criteria for triage biodosimetry. We present high performance ADCI (ADCI-HT), with the requisite throughput to stratify exposures of populations in large scale radiation events.MethodsADCI-HT streamlines dose estimation by optimal scheduling of DC detection, given that the numbers of samples and metaphase cell images in each sample vary. A supercomputer analyzes these data in parallel, with each processor handling a single image at a time. Processor resources are managed hierarchically to maximize a constant stream of sample and image analysis. Metaphase data from populations of individuals with clinically relevant radiation exposures after simulated large nuclear incidents were analyzed. Sample counts were derived from US Census data. Analysis times and exposures were quantified for 15 different scenarios.ResultsProcessing of metaphase images from 1,744 samples (500 images each) used 16,384 CPUs and was completed in 1hr 11min 23sec, with radiation dose of all samples determined in 32 sec with 1,024 CPUs. Processing of 40,000 samples with varying numbers of metaphase cells, 10 different exposures from 5 different biodosimetry labs met IAEA accuracy criteria (dose estimate differences were < 0.5 Gy; median = 0.07) and was completed in ~25 hours. Population-scale metaphase image datasets within radiation contours of nuclear incidents were defined by exposure levels (either >1 Gy or >2 Gy). The time needed to analyze samples of all individuals receiving exposures from a high yield airborne nuclear device ranged from 0.6-7.4 days, depending on the population density.ConclusionADCI-HT delivers timely and accurate dose estimates in a simulated population-scale radiation incident.