216 research outputs found
Respiratory pathogen colonisation of dental plaque, the lower airways and endotracheal tube biofilms during mechanical ventilation
Purpose In mechanically ventilated patients, the endotracheal tube is an essential interface between the patient and ventilator, but inadvertently, it also facilitates the development of ventilator-associated pneumonia (VAP) by subverting pulmonary host defenses. A number of investigations suggest that bacteria colonizing the oral cavity may be important in the etiology of VAP. The present study evaluated microbial changes that occurred in dental plaque and lower airways of 107 critically ill mechanically ventilated patients. Materials and Methods Dental plaque and lower airways fluid was collected during the course of mechanical ventilation, with additional samples of dental plaque obtained during the entirety of patients' hospital stay. Results A âmicrobial shiftâ occurred in dental plaque, with colonization by potential VAP pathogens, namely, Staphylococcus aureus and Pseudomonas aeruginosa in 35 patients. Post-extubation analyses revealed that 70% and 55% of patients whose dental plaque included S aureus and P aeruginosa, respectively, reverted back to having a predominantly normal oral microbiota. Respiratory pathogens were also isolated from the lower airways and within the endotracheal tube biofilms. Conclusions To the best of our knowledge, this is the largest study to date exploring oral microbial changes during both mechanical ventilation and after recovery from critical illness. Based on these findings, it was apparent that during mechanical ventilation, dental plaque represents a source of potential VAP pathogens
Rapid Generation of Kilonova Light Curves Using Conditional Variational Autoencoder
The discovery of the optical counterpart, along with the gravitational waves
from GW170817, of the first binary neutron star merger, opened up a new era for
multi-messenger astrophysics. Combining the GW data with the optical
counterpart, also known as AT2017gfo, classified as a kilonova, has revealed
the nature of compact binary merging systems by extracting enriched information
about the total binary mass, the mass ratio, the system geometry, and the
equation of state. Even though the detection of kilonova brought about a
revolution in the domain of multi-messenger astronomy, since there has been
only one kilonova from a gravitational wave detected binary neutron star merger
event so far, this limits the exact understanding of the origin and propagation
of the kilonova. Here, we use a conditional variational autoencoder trained on
light curve data from two kilonova models having different temporal lengths,
and consequently, generate kilonova light curves rapidly based on physical
parameters of our choice with good accuracy. Once trained, the time scale for
light curve generation is of the order of a few milliseconds, thus speeding up
generating light curves by times compared to the simulation. The mean
squared error between the generated and original light curves is typically
with a maximum of for each set of considered physical parameter;
while having a maximum of error across the whole parameter space.
Hence, implementing this technique provides fast and reliably accurate results.Comment: 19 pages, 7 figures (3 additional figures in appendix), accepted to
Ap
The Australasian dingo archetype: de novo chromosome-length genome assembly, DNA methylome, and cranial morphology
BACKGROUND: One difficulty in testing the hypothesis that the Australasian dingo is a functional intermediate between wild wolves and domesticated breed dogs is that there is no reference specimen. Here we link a high-quality de novo long-read chromosomal assembly with epigenetic footprints and morphology to describe the Alpine dingo female named Cooinda. It was critical to establish an Alpine dingo reference because this ecotype occurs throughout coastal eastern Australia where the first drawings and descriptions were completed.
FINDINGS: We generated a high-quality chromosome-level reference genome assembly (Canfam_ADS) using a combination of Pacific Bioscience, Oxford Nanopore, 10X Genomics, Bionano, and Hi-C technologies. Compared to the previously published Desert dingo assembly, there are large structural rearrangements on chromosomes 11, 16, 25, and 26. Phylogenetic analyses of chromosomal data from Cooinda the Alpine dingo and 9 previously published de novo canine assemblies show dingoes are monophyletic and basal to domestic dogs. Network analyses show that the mitochondrial DNA genome clusters within the southeastern lineage, as expected for an Alpine dingo. Comparison of regulatory regions identified 2 differentially methylated regions within glucagon receptor GCGR and histone deacetylase HDAC4 genes that are unmethylated in the Alpine dingo genome but hypermethylated in the Desert dingo. Morphologic data, comprising geometric morphometric assessment of cranial morphology, place dingo Cooinda within population-level variation for Alpine dingoes. Magnetic resonance imaging of brain tissue shows she had a larger cranial capacity than a similar-sized domestic dog.
CONCLUSIONS: These combined data support the hypothesis that the dingo Cooinda fits the spectrum of genetic and morphologic characteristics typical of the Alpine ecotype. We propose that she be considered the archetype specimen for future research investigating the evolutionary history, morphology, physiology, and ecology of dingoes. The female has been taxidermically prepared and is now at the Australian Museum, Sydney
Evolution of star formation in the UKIDSS ultra deep survey field-I. Luminosity functions and cosmic star formation rate out to z = 1.6
We present new results on the cosmic star formation history in the Subaru/XMM-Newton Deep Survey (SXDS)-Ultra Deep Survey (UDS) field out to z = 1.6. We compile narrowband data from the Subaru Telescope and the Visible and Infrared Survey Telescope forAstronomy (VISTA) in conjunction with broad-band data from the SXDS and UDS, to makea selection of 5725 emission-line galaxies in 12 redshift slices, spanning 10 Gyr of cosmictime. We determine photometric redshifts for the sample using 11-band photometry, and usea spectroscopically confirmed subset to fine tune the resultant redshift distribution. We usethe maximum-likelihood technique to determine luminosity functions in each redshift slice and model the selection effects inherent in any narrow-band selection statistically, to obviatethe retrospective corrections ordinarily required. The deep narrow-band data are sensitive tovery low star formation rates (SFRs), and allow an accurate evaluation of the faint end slopeof the Schechter function, Îą We find that a is particularly sensitive to the assumed faintest broad-band magnitude of a galaxy capable of hosting an emission line, and propose thatthis limit should be empirically motivated. For this analysis, we base our threshold on thelimiting observed equivalent widths of emission lines in the local Universe. We compute thecharacteristic SFR of galaxies in each redshift slice, and the integrated SFR density,Ď SFR. Wefind our results to be in good agreement with the literature and parametrize the evolution of the SFR density as Ď SFR Îą(1 + z)4.58 confirming a steep decline in star formation activity since z ~ 1.6.Peer reviewe
Antioxidant and lipid supplementation improve the development of photoreceptor outer segments in pluripotent stem cell-derived retinal organoids
The generation of retinal organoids from human pluripotent stem cells (hPSC) is now a well-established process that in part recapitulates retinal development. However, hPSC-derived photoreceptors that exhibit well-organized outer segment structures have yet to be observed. To facilitate improved inherited retinal disease modeling, we determined conditions that would support outer segment development in maturing hPSC-derived photoreceptors. We established that the use of antioxidants and BSA-bound fatty acids promotes the formation of membranous outer segment-like structures. Using new protocols for hPSC-derived retinal organoid culture, we demonstrated improved outer segment formation for both rod and cone photoreceptors, including organized stacked discs. Using these enhanced conditions to generate iPSC-derived retinal organoids from patients with X-linked retinitis pigmentosa, we established robust cellular phenotypes that could be ameliorated following adeno-associated viral vector-mediated gene augmentation. These findings should aid both disease modeling and the development of therapeutic approaches for the treatment of photoreceptor disorders
Canfam GSD: De novo chromosome-length genome assembly of the German Shepherd Dog (Canis lupus familiaris) using a combination of long reads, optical mapping, and Hi-C
Background: The German Shepherd Dog (GSD) is one of the most common breeds on earth and has been bred for its utility
and intelligence. It is often first choice for police and military work, as well as protection, disability assistance, and search-and-rescue. Yet, GSDs are well known to be susceptible to a range of genetic diseases that can interfere with their training. Such diseases are of particular concern when they occur later in life, and fully trained animals are not able to continue their duties.
Findings: Here, we provide the draft genome sequence of a healthy German Shepherd female as a
reference for future disease and evolutionary studies. We generated this improved canid reference genome (CanFam GSD)
utilizing a combination of Pacific Bioscience, Oxford Nanopore, 10X Genomics, Bionano, and Hi-C technologies. The GSD
assembly is âź80 times as contiguous as the current canid reference genome (20.9 vs 0.267 Mb contig N50), containing far
fewer gaps (306 vs 23,876) and fewer scaffolds (429 vs 3,310) than the current canid reference genome CanFamv3.1. Two
chromosomes (4 and 35) are assembled into single scaffolds with no gaps. BUSCO analyses of the genome assembly results
show that 93.0% of the conserved single-copy genes are complete in the GSD assembly compared with 92.2% for CanFam
v3.1. Homology-based gene annotation increases this value to âź99%. Detailed examination of the evolutionarily important
pancreatic amylase region reveals that there are most likely 7 copies of the gene, indicative of a duplication of 4 ancestral
copies and the disruption of 1 copy.
Conclusions: GSD genome assembly and annotation were produced with major
improvement in completeness, continuity, and quality over the existing canid reference. This resource will enable further
research related to canine diseases, the evolutionary relationships of canids, and other aspects of canid biology
Rapid generation of kilonova light curves using conditional variational autoencoder
The discovery of the optical counterpart, along with the gravitational waves (GWs) from GW170817, of the first binary neutron star merger has opened up a new era for multimessenger astrophysics. Combining the GW data with the optical counterpart, also known as AT 2017gfo and classified as a kilonova, has revealed the nature of compact binary merging systems by extracting enriched information about the total binary mass, the mass ratio, the system geometry, and the equation of state. Even though the detection of kilonovae has brought about a revolution in the domain of multimessenger astronomy, there has been only one kilonova from a GW-detected binary neutron star merger event confirmed so far, and this limits the exact understanding of the origin and propagation of the kilonova. Here, we use a conditional variational autoencoder (CVAE) trained on light-curve data from two kilonova models having different temporal lengths, and consequently, generate kilonova light curves rapidly based on physical parameters of our choice with good accuracy. Once the CVAE is trained, the timescale for light-curve generation is of the order of a few milliseconds, which is a speedup of the generation of light curves by 1000 times as compared to the simulation. The mean squared error between the generated and original light curves is typically 0.015 with a maximum of 0.08 for each set of considered physical parameters, while having a maximum of â0.6 error across the whole parameter space. Hence, implementing this technique provides fast and reliably accurate results
The trend of disruption in the functional brain network topology of Alzheimerâs disease
Alzheimerâs disease (AD) is a progressive disorder associated with cognitive dysfunction that alters the brainâs functional connectivity. Assessing these alterations has become a topic of increasing interest. However, a few studies have examined different stages of AD from a complex network perspective that cover different topological scales. This study used resting state fMRI data to analyze the trend of functional connectivity alterations from a cognitively normal (CN) state through early and late mild cognitive impairment (EMCI and LMCI) and to Alzheimerâs disease. The analyses had been done at the local (hubs and activated links and areas), meso (clustering, assortativity, and rich-club), and global (small-world, small-worldness, and efficiency) topological scales. The results showed that the trends of changes in the topological architecture of the functional brain network were not entirely proportional to the AD progression. There were network characteristics that have changed non-linearly regarding the disease progression, especially at the earliest stage of the disease, i.e., EMCI. Further, it has been indicated that the diseased groups engaged somatomotor, frontoparietal, and default mode modules compared to the CN group. The diseased groups also shifted the functional network towards more random architecture. In the end, the methods introduced in this paper enable us to gain an extensive understanding of the pathological changes of the AD process
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The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel
<p>Abstract</p> <p>Background</p> <p>Drinking water contaminated with inorganic arsenic is associated with increased risk for different types of cancer. Paradoxically, arsenic trioxide can also be used to induce remission in patients with acute promyelocytic leukemia (APL) with a success rate of approximately 80%. A comprehensive study examining the mechanisms and potential signaling pathways contributing to the anti-tumor properties of arsenic trioxide has not been carried out.</p> <p>Methods</p> <p>Here we applied a systems biology approach to identify gene biomarkers that underlie tumor cell responses to arsenic-induced cytotoxicity. The baseline gene expression levels of 14,500 well characterized human genes were associated with the GI<sub>50</sub> data of the NCI-60 tumor cell line panel from the developmental therapeutics program (DTP) database. Selected biomarkers were tested <it>in vitro</it> for the ability to influence tumor susceptibility to arsenic trioxide.</p> <p>Results</p> <p>A significant association was found between the baseline expression levels of 209 human genes and the sensitivity of the tumor cell line panel upon exposure to arsenic trioxide. These genes were overlayed onto protein-protein network maps to identify transcriptional networks that modulate tumor cell responses to arsenic trioxide. The analysis revealed a significant enrichment for the oxidative stress response pathway mediated by nuclear factor erythroid 2-related factor 2 (NRF2) with high expression in arsenic resistant tumor cell lines. The role of the NRF2 pathway in protecting cells against arsenic-induced cell killing was validated in tumor cells using shRNA-mediated knock-down.</p> <p>Conclusions</p> <p>In this study, we show that the expression level of genes in the NRF2 pathway serve as potential gene biomarkers of tumor cell responses to arsenic trioxide. Importantly, we demonstrate that tumor cells that are deficient for NRF2 display increased sensitivity to arsenic trioxide. The results of our study will be useful in understanding the mechanism of arsenic-induced cytotoxicity in cells, as well as the increased applicability of arsenic trioxide as a chemotherapeutic agent in cancer treatment.</p
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