Miracle-dz/UniFAR-FTUs huggingface dataset:
T. gondii RP Promoters & Knockdown Reveal Molecular Pathways Associated with Proliferation and Cell-Cycle Arrest

Molecular pathways regulating rapid proliferation and persistence are fundamental for pathogens but are not elucidated fully in Toxoplasma gondii. Promoters of T. gondii ribosomal proteins (RPs) were analyzed by EMSAs and ChIP. One RP promoter domain, known to bind an Apetela 2, bound to nuclear extract proteins. Promoter domains appeared to associate with histone acetyl transferases. To study effects of a RP gene's regulation in T. gondii, mutant parasites (Δrps13) were engineered with integration of tetracycline repressor (TetR) response elements in a critical location in the rps13 promoter and transfection of a yellow fluorescent-tetracycline repressor (YFP-TetR). This permitted conditional knockdown of rps13 expression in a tightly regulated manner. Δrps13 parasites were studied in the presence (+ATc) or absence of anhydrotetracycline (-ATc) in culture. -ATc, transcription of the rps13 gene and expression of RPS13 protein were markedly diminished, with concomitant cessation of parasite replication. Study of Δrps13 expressing Myc-tagged RPL22, -ATc, showed RPL22 diminished but at a slower rate. Quantitation of RNA showed diminution of 18S RNA. Depletion of RPS13 caused arrest of parasites in the G1 cell cycle phase, thereby stopping parasite proliferation. Transcriptional differences ±ATc implicate molecules likely to function in regulation of these processes. In vitro, -ATc, Δrps13 persists for months and the proliferation phenotype can be rescued with ATc. In vivo, however, Δrps13 could only be rescued when ATc was given simultaneously and not at any time after 1 week, even when L-NAME and ATc were administered. Immunization with Δrps13 parasites protects mice completely against subsequent challenge with wildtype clonal Type 1 parasites, and robustly protects mice against wildtype clonal Type 2 parasites. Our results demonstrate that G1 arrest by ribosomal protein depletion is associated with persistence of T. gondii in a model system in vitro and immunization with Δrps13 protects mice against subsequent challenge with wildtype parasites.
Strongly hyperbolic Hamiltonian systems in numerical relativity: formulation and symplectic integration

We consider two strongly hyperbolic Hamiltonian formulations of general relativity and their numerical integration with a free and a partially constrained symplectic integrator. In those formulations, we use hyperbolic drivers for the shift and in one case also for the densitized lapse. A system where the densitized lapse is an external field allows us to enforce the momentum constraints in a holonomically constrained Hamiltonian system and to turn the Hamilton constraint function from a weak to a strong invariant. These schemes are tested in a perturbed Minkowski and a Schwarzschild space-time. In those examples, we find advantages of the strongly hyperbolic formulations over the Arnowitt–Deser–Misner (ADM) system presented in [28]. Furthermore, we observe stabilizing effects of the partially constrained evolution in Schwarzschild spacetime as long as the momentum constraints are enforced.
Reciprocal Role of ERK and Nf-κb Pathways in Survival and Activation of Osteoclasts

To examine the role of mitogen-activated protein kinase and nuclear factor kappa B (NF-κB) pathways on osteoclast survival and activation, we constructed adenovirus vectors carrying various mutants of signaling molecules: dominant negative Ras (RasDN), constitutively active MEK1 (MEKCA), dominant negative IκB kinase 2 (IKKDN), and constitutively active IKK2 (IKKCA). Inhibiting ERK activity by RasDN overexpression rapidly induced the apoptosis of osteoclast-like cells (OCLs) formed in vitro, whereas ERK activation after the introduction of MEKCA remarkably lengthened their survival by preventing spontaneous apoptosis. Neither inhibition nor activation of ERK affected the bone-resorbing activity of OCLs. Inhibition of NF-κB pathway with IKKDN virus suppressed the pit-forming activity of OCLs and NF-κB activation by IKKCA expression upregulated it without affecting their survival. Interleukin 1α (IL-1α) strongly induced ERK activation as well as NF-κB activation. RasDN virus partially inhibited ERK activation, and OCL survival promoted by IL-1α. Inhibiting NF-κB activation by IKKDN virus significantly suppressed the pit-forming activity enhanced by IL-1α. These results indicate that ERK and NF-κB regulate different aspects of osteoclast activation: ERK is responsible for osteoclast survival, whereas NF-κB regulates osteoclast activation for bone resorption.
Anticancer chemosensitization and radiosensitization by the novel poly(ADP-ribose) polymerase-1 inhibitor AG14361.

BACKGROUND Poly(ADP-ribose) polymerase-1 (PARP-1) facilitates the repair of DNA strand breaks. Inhibiting PARP-1 increases the cytotoxicity of DNA-damaging chemotherapy and radiation therapy in vitro. Because classical PARP-1 inhibitors have limited clinical utility, we investigated whether AG14361, a novel potent PARP-1 inhibitor (inhibition constant <5 nM), enhances the effects of chemotherapy and radiation therapy in human cancer cell cultures and xenografts. METHODS The effect of AG14361 on the antitumor activity of the DNA alkylating agent temozolomide, topoisomerase I poisons topotecan or irinotecan, or x-irradiation or gamma-radiation was investigated in human cancer cell lines A549, LoVo, and SW620 by proliferation and survival assays and in xenografts in mice by tumor volume determination. The specificity of AG14361 for PARP-1 was investigated by microarray analysis and by antiproliferation and acute toxicity assays in PARP-1-/- and PARP-1+/+ cells and mice. After intraperitoneal administration, the concentration of AG14361 was determined in mouse plasma and tissues, and its effect on PARP-1 activity was determined in tumor homogenates. All statistical tests were two-sided. RESULTS AG14361 at 0.4 micro M did not affect cancer cell gene expression or growth, but it did increase the antiproliferative activity of temozolomide (e.g., in LoVo cells by 5.5-fold, 95% confidence interval [CI] = 4.9-fold to 5.9-fold; P =.004) and topotecan (e.g., in LoVo cells by 1.6-fold, 95% CI = 1.3-fold to 1.9-fold; P =.002) and inhibited recovery from potentially lethal gamma-radiation damage in LoVo cells by 73% (95% CI = 48% to 98%). In vivo, nontoxic doses of AG14361 increased the delay of LoVo xenograft growth induced by irinotecan, x-irradiation, or temozolomide by two- to threefold. The combination of AG14361 and temozolomide caused complete regression of SW620 xenograft tumors. AG14361 was retained in xenografts in which PARP-1 activity was inhibited by more than 75% for at least 4 hours. CONCLUSION AG14361 is, to our knowledge, the first high-potency PARP-1 inhibitor with the specificity and in vivo activity to enhance chemotherapy and radiation therapy of human cancer.
Coevolution between Nuclear-Encoded DNA Replication, Recombination, and Repair Genes and Plastid Genome Complexity

Disruption of DNA replication, recombination, and repair (DNA-RRR) systems has been hypothesized to cause highly elevated nucleotide substitution rates and genome rearrangements in the plastids of angiosperms, but this theory remains untested. To investigate nuclear–plastid genome (plastome) coevolution in Geraniaceae, four different measures of plastome complexity (rearrangements, repeats, nucleotide insertions/deletions, and substitution rates) were evaluated along with substitution rates of 12 nuclear-encoded, plastid-targeted DNA-RRR genes from 27 Geraniales species. Significant correlations were detected for nonsynonymous (dN) but not synonymous (dS) substitution rates for three DNA-RRR genes (uvrB/C, why1, and gyrA) supporting a role for these genes in accelerated plastid genome evolution in Geraniaceae. Furthermore, correlation between dN of uvrB/C and plastome complexity suggests the presence of nucleotide excision repair system in plastids. Significant correlations were also detected between plastome complexity and 13 of the 90 nuclear-encoded organelle-targeted genes investigated. Comparisons revealed significant acceleration of dN in plastid-targeted genes of Geraniales relative to Brassicales suggesting this correlation may be an artifact of elevated rates in this gene set in Geraniaceae. Correlation between dN of plastid-targeted DNA-RRR genes and plastome complexity supports the hypothesis that the aberrant patterns in angiosperm plastome evolution could be caused by dysfunction in DNA-RRR systems.
Green Synthesis and Antibacterial Effect of Silver Nanoparticles Using Vitex Negundo L.

Different biological methods are gaining recognition for the production of silver nanoparticles (Ag-NPs) due to their multiple applications. One of the most important applications of Ag-NPs is their use as an anti-bacterial agent. The use of plants in the synthesis of nanoparticles emerges as a cost effective and eco-friendly approach. In this study the biosynthesis of silver nanoparticles using Vitex negundo L. extract and its antimicrobial properties has been reported. The resulting silver particles are characterized using transmission electron microscopy (TEM), X-ray diffraction (XRD) and UV–Visible (UV-Vis) spectroscopic techniques. The TEM study showed the formation of silver nanoparticles in the 10–30 nm range and average 18.2 nm in size. The XRD study showed that the particles are crystalline in nature, with a face centered cubic (fcc) structure. The silver nanoparticles showed the antimicrobial activity against Gram positive and Gram negative bacteria. Vitex negundo L. was found to display strong potential for the synthesis of silver nanoparticles as antimicrobial agents by rapid reduction of silver ions (Ag+ to Ag0).
Image classification based on segmentation-free object recognition

This paper presents a new method for categorical classification. A method called two-dimensional continuous dynamic programming (2DCDP) is adopted to optimally capture the corresponding pixels within nonlinearly matched areas in an input image and a reference image representing an object without advance segmentation procedure. Then an image can be converted into a direction pattern which is made by matching pixels between a reference image and an input image. Finally, the category of the test image is deemed to be that which has the strongest correlation with the learning images. Experimental results show that the proposed method achieves a competitive performance on the Caltech 101 image dataset.
Audiovisual synchrony enhances BOLD responses in a brain network including multisensory STS while also enhancing target‐detection performance for both modalities

The brain seeks to combine related inputs from different senses (e.g., hearing and vision), via multisensory integration. Temporal information can indicate whether stimuli in different senses are related or not. A recent human fMRI study (Noesselt et al. [2007]: J Neurosci 27:11431–11441) used auditory and visual trains of beeps and flashes with erratic timing, manipulating whether auditory and visual trains were synchronous or unrelated in temporal pattern. A region of superior temporal sulcus (STS) showed higher BOLD signal for the synchronous condition. But this could not be related to performance, and it remained unclear if the erratic, unpredictable nature of the stimulus trains was important. Here we compared synchronous audiovisual trains to asynchronous trains, while using a behavioral task requiring detection of higher‐intensity target events in either modality. We further varied whether the stimulus trains had predictable temporal pattern or not. Synchrony (versus lag) between auditory and visual trains enhanced behavioral sensitivity (d') to intensity targets in either modality, regardless of predictable versus unpredictable patterning. The analogous contrast in fMRI revealed BOLD increases in several brain areas, including the left STS region reported by Noesselt et al. [2007: J Neurosci 27:11431–11441]. The synchrony effect on BOLD here correlated with the subject‐by‐subject impact on performance. Predictability of temporal pattern did not affect target detection performance or STS activity, but did lead to an interaction with audiovisual synchrony for BOLD in inferior parietal cortex. Hum Brain Mapp, 2011. © 2011 Wiley‐Liss, Inc.
Quantifiable Biomarkers of Normal Aging in the Japanese Medaka Fish (Oryzias latipes)

Background Small laboratory fish share many anatomical and histological characteristics with other vertebrates, yet can be maintained in large numbers at low cost for lifetime studies. Here we characterize biomarkers associated with normal aging in the Japanese medaka (Oryzias latipes), a species that has been widely used in toxicology studies and has potential utility as a model organism for experimental aging research. Principal Findings The median lifespan of medaka was approximately 22 months under laboratory conditions. We performed quantitative histological analysis of tissues from age-grouped individuals representing young adults (6 months old), mature adults (16 months old), and adults that had survived beyond the median lifespan (24 months). Livers of 24-month old individuals showed extensive morphologic changes, including spongiosis hepatis, steatosis, ballooning degeneration, inflammation, and nuclear pyknosis. There were also phagolysosomes, vacuoles, and residual bodies in parenchymal cells and congestion of sinusoidal vessels. Livers of aged individuals were characterized by increases in lipofuscin deposits and in the number of TUNEL-positive apoptotic cells. Some of these degenerative characteristics were seen, to a lesser extent, in the livers of 16-month old individuals, but not in 6-month old individuals. The basal layer of the dermis showed an age-dependent decline in the number of dividing cells and an increase in senescence-associated β-galactosidase. The hearts of aged individuals were characterized by fibrosis and lipofuscin deposition. There was also a loss of pigmented cells from the retinal epithelium. By contrast, age-associated changes were not apparent in skeletal muscle, the ocular lens, or the brain. Significance The results provide a set of markers that can be used to trace the process of normal tissue aging in medaka and to evaluate the effect of environmental stressors.
The cost of seeing the meaning: Conceptual processing of distractors triggers localized target suppression

ABSTRACT It is often assumed that conceptual information impacts visual experience only after perceptual information has been extracted. However, the present study suggests that conceptual processing can interfere with perceptual processes, as reflected in target perception impairments that are specific to the location of conceptually salient distractors. Experiment 1 replicated previous findings that emotional distractors in a rapid serial visual presentation cause a spontaneous, spatially localized impairment in target perception, further finding that distractors that are merely featurally salient do not. Experiment 2 suggested that conceptually salient distractors that are non-emotional also elicit such spatially localized impairments, which are shorter lived than those following emotional distractors. Experiment 3 suggested that featurally salient distractors that are not conceptually salient engage a different, spatial attention mechanism. Together, these findings suggest that, whereas featurally salient distractors can capture spatial attention, conceptual distractors additionally engage mechanisms that suppress spatiotemporally competing targets.
Reporter genes lucFF, luxCDABE, gfp, and dsred have different characteristics in whole-cell bacterial sensors.

The selection of a genetic reporter can be difficult because of the wide range of genes available. In order to reduce the selection, we compared the performance of different reporter genes: firefly luciferase (Photinus pyralis lucFF), bacterial luciferase operon (Photorhabdus luminescens luxCDABE), green fluorescent protein (Aequorea victoria gfp), and red fluorescent protein (Discosoma sp. dsred) in whole-cell bacterial sensors. Escherichia coli sensor bacteria were engineered to contain a reporter plasmid that carries the reporter gene under the control of mercury- (mer from Tn21) or arsenite- (ars from R773) responsive regulatory units. Characteristics of the strains were studied by using different arsenite or mercury concentrations and incubation times. The lowest detectable concentration of analytes and the fastest responses were achieved with lucFF or luxCDABE as reporter genes. The fluorescent proteins, GFP and DsRed, gave responses at higher analyte concentrations and after significantly longer incubation times. The results indicate that luciferases are better reporters in whole-cell sensor bacteria.
AAV-Mediated Clarin-1 Expression in the Mouse Retina: Implications for USH3A Gene Therapy

Usher syndrome type III (USH3A) is an autosomal recessive disorder caused by mutations in clarin-1 (CLRN1) gene, leading to progressive retinal degeneration and sensorineural deafness. Efforts to develop therapies for preventing photoreceptor cell loss are hampered by the lack of a retinal phenotype in the existing USH3 mouse models and by conflicting reports regarding the endogenous retinal localization of clarin-1, a transmembrane protein of unknown function. In this study, we used an AAV-based approach to express CLRN1 in the mouse retina in order to determine the pattern of its subcellular localization in different cell types. We found that all major classes of retinal cells express AAV-delivered CLRN1 driven by the ubiquitous, constitutive small chicken β-actin promoter, which has important implications for the design of future USH3 gene therapy studies. Within photoreceptor cells, AAV-expressed CLRN1 is mainly localized at the inner segment region and outer plexiform layer, similar to the endogenous expression of other usher proteins. Subretinal delivery using a full strength viral titer led to significant loss of retinal function as evidenced by ERG analysis, suggesting that there is a critical limit for CLRN1 expression in photoreceptor cells. Taken together, these results suggest that CLRN1 expression is potentially supported by a variety of retinal cells, and the right combination of AAV vector dose, promoter, and delivery method needs to be selected to develop safe therapies for USH3 disorder.
Understanding technology acceptance by older adults who are aging in place: A dynamic perspective

Background There is a growing interest in empowering older adults to age-inplace by deploying various types of technology (i.e., eHealth, Ambient Assisted Living technology, Smart Home technology, and Gerontechnology). However, initiatives aimed at implementing these technologies are complicated by the fact that multiple stakeholder groups are involved. Goals and motives of stakeholders may not always be transparent or aligned, yet research on convergent and divergent positions of stakeholders is scarce. Objective To provide insight into the positions of stakeholder groups involved in the implementation of technology for aging-in-place; what kind of technology do they see as relevant, what do they aim to achieve by implementing technology, and what is needed to achieve successful implementations? Methods Monodisciplinary focus groups were conducted with participants (N = 29) representing five groups of stakeholders: older adults (n = 6), care professionals (n = 7), managers within home care or social work organizations (n = 5), technology designers and suppliers (n = 6), and policy makers (n = 5). Transcripts were analyzed using thematic analysis. Results Stakeholders considered 26 different types of technologies to be relevant for enabling independent living. Only six types of technology were mentioned by all stakeholder groups. Care professionals mentioned fewer different types of technology than other groups. All stakeholder groups felt that the implementation of technology for aging-inplace can be considered a success when: (1) older adults’ needs and wishes are prioritized during development and deployment of the technology; (2) the technology is accepted by older adults; (3) the technology provides benefits to older adults; and (4) favorable prerequisites for the use of technology by older adults exist. While stakeholders seemed to have identical aims, several underlying differences emerged, for example with regards to who should pay for technology. Additionally, each stakeholder group mentioned specific steps that need to be taken to achieve successful implementation. Collectively, stakeholders feel they need to take the leap (i.e., change attitudes, change policies, collaborate with other organizations); bridge the gap (i.e., match technology with individuals, stimulate interdisciplinary education); facilitate technology for the masses (i.e., work on products and research that supports large-scale rollouts, train target groups on how to use technology); and take time to reflect (i.e., evaluate use and outcomes). Conclusions Stakeholders largely agree on the direction in which they should be heading; however, they have different perspectives with regards to the technologies that can be
Capture of Auditory Motion by Vision Is Represented by an Activation Shift from Auditory to Visual Motion Cortex

The brain is capable of integrating motion information arising from visual and auditory input. Such integration between sensory modalities can aid one another and helps to stabilize the motion percept. However, if motion information differs between sensory modalities, it can also result in an illusory auditory motion percept. This phenomenon is referred to as the cross-modal dynamic capture (CDC) illusion. We used functional magnetic resonance imaging to investigate whether early visual and auditory motion areas are involved in the generation of this illusion. Among the trials containing conflicting audiovisual motion, we compared the trials in which CDC occurred to those in which it did not and used a region of interest approach to see whether the auditory motion complex (AMC) and the visual motion area hMT/V5+ were affected by this illusion. Our results show that CDC reduces activation in bilateral auditory motion areas while increasing activity in the bilateral hMT/V5+. Interestingly, our data show that the CDC illusion is preceded by an enhanced activation that is most dominantly present in the ventral intraparietal sulcus. Moreover, we assessed the effect of motion coherency, which was found to enhance activation in bilateral hMT/V5+ as well as in an area adjacent to the right AMC. Together, our results show that audiovisual integration occurs in early motion areas. Furthermore, it seems that the cognitive state of subjects before stimulus onset plays an important role in the generation of multisensory illusions.
GPU-Accelerated Real-Time Stixel Computation

The Stixel World is a medium-level, compact representation of road scenes that abstracts millions of disparity pixels into hundreds or thousands of stixels. The goal of this work is to implement and evaluate a complete multistixel estimation pipeline on an embedded, energy-efficient, GPU-accelerated device. This work presents a full GPUaccelerated implementation of stixel estimation that produces reliable results at 26 frames per second (real-time) on the Tegra X1 for disparity images of 1024×440 pixels and stixel widths of 5 pixels, and achieves more than 400 frames per second on a high-end Titan X GPU card.