ToxoNet: A high confidence map of protein-protein interactions in Toxoplasma gondii.

The apicomplexan intracellular parasite Toxoplasma gondii is a major food borne pathogen that is highly prevalent in the global population. The majority of the T. gondii proteome remains uncharacterized and the organization of proteins into complexes is unclear. To overcome this knowledge gap, we used a biochemical fractionation strategy to predict interactions by correlation profiling. To overcome the deficit of high-quality training data in non-model organisms, we complemented a supervised machine learning strategy, with an unsupervised approach, based on similarity network fusion. The resulting combined high confidence network, ToxoNet, comprises 2,063 interactions connecting 652 proteins. Clustering identifies 93 protein complexes. We identified clusters enriched in mitochondrial machinery that include previously uncharacterized proteins that likely represent novel adaptations to oxidative phosphorylation. Furthermore, complexes enriched in proteins localized to secretory organelles and the inner membrane complex, predict additional novel components representing novel targets for detailed functional characterization. We present ToxoNet as a publicly available resource with the expectation that it will help drive future hypotheses within the research community.

Ultra-high-resolution spectral silicon-based photon-counting detector CT for coronary CT angiography: Initial results in a dynamic phantom.

BACKGROUND: Recent improvements in CT detector technology have led to smaller detector pixels resolving frequencies beyond 20 lp/cm and enabled ultra-high-resolution CT. Silicon-based photon-counting detector (PCD) CT is one such technology that promises improved spatial and spectral resolution. However, when the detector pixel sizes are reduced, the impact of cardiac motion on CT images becomes more pronounced. Here, we investigated the effects cardiac motion on the image quality of a clinical prototype Si-PCD scanner in a dynamic heart phantom. METHODS: A series of 3D-printed vessels were created to simulate coronary arteries with diameter in the 1-3.5 â€‹mm range. Four coronary stents were set inside the d â€‹= â€‹3.5 â€‹mm vessels and all vessels were filled with contrast agents and were placed inside a dynamic cardiac phantom. The phantom was scanned in motion (60 bpm) and at rest on a prototype clinical Si-PCD CT scanner in 8-bin spectral UHR mode. Virtual monoenergetic images (VMI) were generated at 70 â€‹keV and CT number accuracy and effective spatial resolution (blooming) of rest and motion VMIs were compared. RESULTS: Linear regression analysis of CT numbers showed excellent agreement (r â€‹> â€‹0.99) between rest and motion. We did not observe a significant difference (p â€‹> â€‹0.48) in estimating free lumen diameters. Differences in in-stent lumen diameter and stent strut thickness were non-significant with maximum mean difference of approximately 70 â€‹µm. CONCLUSION: We found no significant degradation in CT number accuracy or spatial resolution due to cardiac motion. The results demonstrate the potential of spectral UHR coronary CT angiography enabled by Si-PCD.

Analysis of Wildfire Visualization Systems for Research and Training: Are They up for the Challenge of the Current State of Wildfires?

Wildfires affect many regions across the world. The accelerated progression of global warming has amplified their frequency and scale, deepening their impact on human life, the economy, and the environment. The temperature rise has been driving wildfires to behave unpredictably compared to those previously observed, challenging researchers and fire management agencies to understand the factors behind this behavioral change. Furthermore, this change has rendered fire personnel training outdated and lost its ability to adequately prepare personnel to respond to these new fires. Immersive visualization can play a key role in tackling the growing issue of wildfires. Therefore, this survey reviews various studies that use immersive and non-immersive data visualization techniques to depict wildfire behavior and train first responders and planners. This paper identifies the most useful characteristics of these systems. While these studies support knowledge creation for certain situations, there is still scope to comprehensively improve immersive systems to address the unforeseen dynamics of wildfires.

Assessment of Wellbeing and Anxiety-related Disorders in Those Seeking Rhinoplasty: A Crowdsourcing-based Study.

BACKGROUND: Recently, it has been proposed that psychosocial concerns may motivate the demand for aesthetic rhinoplasty. Although successful operations often improve the quality of life and self-esteem symptoms in patients with sound mental health, they may actually result in unsatisfactory outcomes in those patients with significant depression, anxiety, or other severe psychological disorders. The purpose of this study was to assess the incidence of psychological disorders in patients seeking rhinoplasty. METHODS: A prospective cross-sectional study of 298 random volunteers was conducted, with each participant completing a survey instrument that was administered through an internet crowd-sourcing service (Amazon Mechanical Turk). Participants were asked to complete a 10-item standardized SHNOS scale, and a 26-question PRIME-MD questionnaire in order to assess functional and aesthetic need for rhinoplasty, and the incidence of psychological disorders respectively. RESULTS: 38.95% of female participants reported a willingness to undergo aesthetic rhinoplasty, with a significantly lower number of men reporting the same (27.78%, P = 0.042). Adults between the ages of 18-24 (52.92%) were more willing to undergo aesthetic rhinoplasty, as compared to any other age group (P < 0.01). It was found that 57.84% of patients interested in surgery reported a psychological disorder as determined by the PRIME-MD questionnaire. CONCLUSIONS: Those suffering from major depressive disorder, generalized anxiety disorder, or body dysmorphic disorder may seek aesthetic rhinoplasty as a solution. It is important that surgeons assess patient mental health prior to treatment in order to avoid unsuccessful outcomes secondary to psychosocial illness.

Technical Note: Phantom study to evaluate the dose and image quality effects of a computed tomography organ-based tube current modulation technique.

PURPOSE: This technical note quantifies the dose and image quality performance of a clinically available organ-dose-based tube current modulation (ODM) technique, using experimental and simulation phantom studies. The investigated ODM implementation reduces the tube current for the anterior source positions, without increasing current for posterior positions, although such an approach was also evaluated for comparison. METHODS: Axial CT scans at 120 kV were performed on head and chest phantoms on an ODM-equipped scanner (Optima CT660, GE Healthcare, Chalfont St. Giles, England). Dosimeters quantified dose to breast, lung, heart, spine, eye lens, and brain regions for ODM and 3D-modulation (SmartmA) settings. Monte Carlo simulations, validated with experimental data, were performed on 28 voxelized head phantoms and 10 chest phantoms to quantify organ dose and noise standard deviation. The dose and noise effects of increasing the posterior tube current were also investigated. RESULTS: ODM reduced the dose for all experimental dosimeters with respect to SmartmA, with average dose reductions across dosimeters of 31% (breast), 21% (lung), 24% (heart), 6% (spine), 19% (eye lens), and 11% (brain), with similar results for the simulation validation study. In the phantom library study, the average dose reduction across all phantoms was 34% (breast), 20% (lung), 8% (spine), 20% (eye lens), and 8% (brain). ODM increased the noise standard deviation in reconstructed images by 6%-20%, with generally greater noise increases in anterior regions. Increasing the posterior tube current provided similar dose reduction as ODM for breast and eye lens, increased dose to the spine, with noise effects ranging from 2% noise reduction to 16% noise increase. At noise equal to SmartmA, ODM increased the estimated effective dose by 4% and 8% for chest and head scans, respectively. Increasing the posterior tube current further increased the effective dose by 15% (chest) and 18% (head) relative to SmartmA. CONCLUSIONS: ODM reduced dose in all experimental and simulation studies over a range of phantoms, while increasing noise. The results suggest a net dose/noise benefit for breast and eye lens for all studied phantoms, negligible lung dose effects for two phantoms, increased lung dose and/or noise for eight phantoms, and increased dose and/or noise for brain and spine for all studied phantoms compared to the reference protocol.

Trichomonas vaginalis homolog of macrophage migration inhibitory factor induces prostate cell growth, invasiveness, and inflammatory responses.

The human-infective parasite Trichomonas vaginalis causes the most prevalent nonviral sexually transmitted infection worldwide. Infections in men may result in colonization of the prostate and are correlated with increased risk of aggressive prostate cancer. We have found that T. vaginalis secretes a protein, T. vaginalis macrophage migration inhibitory factor (TvMIF), that is 47% similar to human macrophage migration inhibitory factor (HuMIF), a proinflammatory cytokine. Because HuMIF is reported to be elevated in prostate cancer and inflammation plays an important role in the initiation and progression of cancers, we have explored a role for TvMIF in prostate cancer. Here, we show that TvMIF has tautomerase activity, inhibits macrophage migration, and is proinflammatory. We also demonstrate that TvMIF binds the human CD74 MIF receptor with high affinity, comparable to that of HuMIF, which triggers activation of ERK, Akt, and Bcl-2-associated death promoter phosphorylation at a physiologically relevant concentration (1 ng/mL, 80 pM). TvMIF increases the in vitro growth and invasion through Matrigel of benign and prostate cancer cells. Sera from patients infected with T. vaginalis are reactive to TvMIF, especially in males. The presence of anti-TvMIF antibodies indicates that TvMIF is released by the parasite and elicits host immune responses during infection. Together, these data indicate that chronic T. vaginalis infections may result in TvMIF-driven inflammation and cell proliferation, thus triggering pathways that contribute to the promotion and progression of prostate cancer.

A dynamin-related protein contributes to Trichomonas vaginalis hydrogenosomal fission.

Trichomonas vaginalis is a highly divergent, unicellular eukaryote of the phylum Metamonada, class Parabasalia, and the source of a common sexually transmitted infection. This parasite lacks mitochondria, but harbors an evolutionarily related organelle, the hydrogenosome. We explored the role of dynamin-related proteins (DRPs) in the division of the hydrogenosome. Eight DRP homologues [T. vaginalis DRPs (TvDRPs)], which can be grouped into 3 subclasses, are present in T. vaginalis. We examined 5 TvDRPs that are representative of each subclass, by introducing dominant negative mutations analogous to those known to interfere with mitochondrial division in yeast, worms, and mammals. Microscopic and cell fractionation analyses of parasites expressing one of the mutated TvDRPs (TVAG_350040) demonstrated that this protein localizes to hydrogenosomes. Moreover, these organelles were found to be increased in size and reduced in number in cells expressing this dominant negative protein, relative to parasites expressing the corresponding wild-type TvDRP, the other 4 mutant TvDRPs, or an empty vector control. Our data indicate a role for a TvDRP in the fission of T. vaginalis hydrogenosomes, similar to that described for peroxisomes and mitochondria. These findings reveal a conservation of core components involved in the division of diverse eukaryotic organelles across broad phylogenetic distances.

The effects of gantry tilt on breast dose and image noise in cardiac CT.

PURPOSE: This study investigated the effects of tilted-gantry acquisition on image noise and glandular breast dose in females during cardiac computed tomography (CT) scans. Reducing the dose to glandular breast tissue is important due to its high radiosensitivity and limited diagnostic significance in cardiac CT scans. METHODS: Tilted-gantry acquisition was investigated through computer simulations and experimental measurements. Upon IRB approval, eight voxelized phantoms were constructed from previously acquired cardiac CT datasets. Monte Carlo simulations quantified the dose deposited in glandular breast tissue over a range of tilt angles. The effects of tilted-gantry acquisition on breast dose were measured on a clinical CT scanner (CT750HD, GE Healthcare) using an anthropomorphic phantom with MOSFET dosimeters in the breast regions. In both simulations and experiments, scans were performed at gantry tilt angles of 0°-30°, in 5° increments. The percent change in breast dose was calculated relative to the nontilted scan for all tilt angles. The percent change in noise standard deviation due to gantry tilt was calculated in all reconstructed simulated and experimental images. RESULTS: Tilting the gantry reduced the breast dose in all simulated and experimental phantoms, with generally greater dose reduction at increased gantry tilts. For example, at 30° gantry tilt, the dosimeters located in the superior, middle, and inferior breast regions measured dose reductions of 74%, 61%, and 9%, respectively. The simulations estimated 0%-30% total breast dose reduction across the eight phantoms and range of tilt angles. However, tilted-gantry acquisition also increased the noise standard deviation in the simulated phantoms by 2%-50% due to increased pathlength through the iodine-filled heart. The experimental phantom, which did not contain iodine in the blood, demonstrated decreased breast dose and decreased noise at all gantry tilt angles. CONCLUSIONS: Tilting the gantry reduced the dose to the breast, while also increasing noise standard deviation. Overall, the noise increase outweighed the dose reduction for the eight voxelized phantoms, suggesting that tilted gantry acquisition may not be beneficial for reducing breast dose while maintaining image quality.

Trichomonas vaginalis exosomes deliver cargo to host cells and mediate host∶parasite interactions.

Trichomonas vaginalis is a common sexually transmitted parasite that colonizes the human urogential tract where it remains extracellular and adheres to epithelial cells. Infections range from asymptomatic to highly inflammatory, depending on the host and the parasite strain. Here, we use a combination of methodologies including cell fractionation, immunofluorescence and electron microscopy, RNA, proteomic and cytokine analyses and cell adherence assays to examine pathogenic properties of T. vaginalis. We have found that T.vaginalis produces and secretes microvesicles with physical and biochemical properties similar to mammalian exosomes. The parasite-derived exosomes are characterized by the presence of RNA and core, conserved exosomal proteins as well as parasite-specific proteins. We demonstrate that T. vaginalis exosomes fuse with and deliver their contents to host cells and modulate host cell immune responses. Moreover, exosomes from highly adherent parasite strains increase the adherence of poorly adherent parasites to vaginal and prostate epithelial cells. In contrast, exosomes from poorly adherent strains had no measurable effect on parasite adherence. Exosomes from parasite strains that preferentially bind prostate cells increased binding of parasites to these cells relative to vaginal cells. In addition to establishing that parasite exosomes act to modulate host∶parasite interactions, these studies are the first to reveal a potential role for exosomes in promoting parasite∶parasite communication and host cell colonization.

Circular tomosynthesis: potential in imaging of breast and upper cervical spine--preliminary phantom and in vitro study.

Phantom and in vitro studies were performed to evaluate the potential application of digital circular tomosynthesis in imaging of the breast and upper cervical spine. A prototype volumetric x-ray system was used to image a mammographic phantom, a fresh mastectomy specimen, and a head phantom containing the upper cervical spine. Results show that breast tissue visualization is improved by the ability to produce sectional images that blur overlying structures and yield three-dimensional information about calcification clusters. In upper cervical spine imaging, digital circular tomosynthesis effectively blurs overlying jaw and skull structures so that C1 and C2 can be visualized in a standard anteroposterior view.