677 research outputs found
Blind Source Separation of Hemodynamics from Magnetic Resonance Perfusion Brain Images Using Independent Factor Analysis
Perfusion magnetic resonance brain imaging induces temporal signal changes on brain tissues, manifesting distinct blood-supply patterns for the profound analysis of cerebral hemodynamics. We employed independent factor analysis to blindly separate such dynamic images into different maps, that is, artery, gray matter, white matter, vein and sinus, and choroid plexus, in conjunction with corresponding signal-time curves. The averaged signal-time curve on the segmented arterial area was further used to calculate the relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), and mean transit time (MTT). The averaged ratios for rCBV, rCBF, and MTT between gray and white matters for normal subjects were congruent with those in the literature
Effect of Influenza Vaccination on Mortality and Risk of Hospitalization in Elderly Individuals with and without Disabilities: A Nationwide, Population-Based Cohort Study
Purpose: The effects of influenza vaccines are unclear for elderly individuals with disabilities. We use a population-based cohort study to estimate the effects of influenza vaccines in elderly individuals with and without disabilities. Methods: Data were taken from the National Health Insurance Research Database and Disabled Population Profile of Taiwan. A total of 2,741,403 adults aged 65 or older were identified and 394,490 were people with a disability. These two groups were further divided into those who had or had not received an influenza vaccine. Generalized estimating equations (GEE) were used to compare the relative risks (RRs) of death and hospitalization across the four groups. Results: 30.78% elderly individuals without a disability and 34.59% elderly individuals with a disability had vaccinated for influenza. Compared to the unvaccinated elderly without a disability, the vaccinated elderly without a disability had significantly lower risks in all-cause mortality (RR = 0.64) and hospitalization for any of the influenza-related diseases (RR = 0.91). Both the unvaccinated and vaccinated elderly with a disability had significantly higher risks in all-cause mortality (RR = 1.81 and 1.18, respectively) and hospitalization for any of the influenza-related diseases (RR = 1.73 and 1.59, respectively). Conclusions: The elderly with a disability had higher risks in mortality and hospitalization than those without a disability; however, receiving influenza vaccinations could still generate more protection to the disabled elderl
Multiplex immunofluorescence-guided laser capture microdissection for spatial transcriptomics of metastatic melanoma tissues.
We describe a pipeline for optimized and streamlined multiplexed immunofluorescence-guided laser capture microdissection allowing the harvest of individual cells based on their phenotype and tissue localization for transcriptomic analysis with next-generation RNA sequencing. Here, we analyze transcriptomes of CD3+ T cells, CD14+ monocytes/macrophages, and melanoma cells in non-dissociated metastatic melanoma tissue. While this protocol is described for melanoma tissues, we successfully applied it to human tonsil, skin, and breast cancer tissues as well as mouse lung tissues. For complete details on the use and execution of this protocol, please refer to Martinek et al. (2022)
Hyperbaric oxygen upregulates cochlear constitutive nitric oxide synthase
<p>Abstract</p> <p>Background</p> <p>Hyperbaric oxygen therapy (HBOT) is a known adjuvant for treating ischemia-related inner ear diseases. Controversies still exist in the role of HBOT in cochlear diseases. Few studies to date have investigated the cellular changes that occur in inner ears after HBOT. Nitric oxide, which is synthesized by nitric oxide synthase (NOS), is an important signaling molecule in cochlear physiology and pathology. Here we investigated the effects of hyperbaric oxygen on eardrum morphology, cochlear function and expression of NOS isoforms in cochlear substructures after repetitive HBOT in guinea pigs.</p> <p>Results</p> <p>Minor changes in the eardrum were observed after repetitive HBOT, which did not result in a significant hearing threshold shift by tone burst auditory brainstem responses. A differential effect of HBOT on the expression of NOS isoforms was identified. Upregulation of constitutive NOS (nNOS and eNOS) was found in the substructures of the cochlea after HBOT, but inducible NOS was not found in normal or HBOT animals, as shown by immunohistochemistry. There was no obvious DNA fragmentation present in this HBOT animal model.</p> <p>Conclusions</p> <p>The present evidence indicates that the customary HBOT protocol may increase constitutive NOS expression but such upregulation did not cause cell death in the treated cochlea. The cochlear morphology and auditory function are consequently not changed through the protocol.</p
AMiBA Wideband Analog Correlator
A wideband analog correlator has been constructed for the Yuan-Tseh Lee Array
for Microwave Background Anisotropy. Lag correlators using analog multipliers
provide large bandwidth and moderate frequency resolution. Broadband IF
distribution, backend signal processing and control are described. Operating
conditions for optimum sensitivity and linearity are discussed. From
observations, a large effective bandwidth of around 10 GHz has been shown to
provide sufficient sensitivity for detecting cosmic microwave background
variations.Comment: 28 pages, 23 figures, ApJ in press
Protocol for establishing primary human lung organoid-derived air-liquid interface cultures from cryopreserved human lung tissue.
Primary human lung organoid-derived air-liquid interface (ALI) cultures serve as a physiologically relevant model to study human airway epithelium in vitro. Here, we present a protocol for establishing these cultures from cryopreserved human lung tissue. We describe steps for lung tissue cryostorage, tissue dissociation, lung epithelial organoid generation, and ALI culture differentiation. We also include quality control steps and technical readouts for monitoring virus response. This protocol demonstrates severe acute respiratory syndrome coronavirus 2 infection in these cultures as an example of their utility. For complete details on the use and execution of this protocol, please refer to Diana Cadena Castaneda et al. (2023)
Exploring the Mechanism Responsible for Cellulase Thermostability by Structure-Guided Recombination
Cellulases from Bacillus and Geobacillus bacteria are potentially useful in the biofuel and animal feed industries. One of the unique characteristics of these enzymes is that they are usually quite thermostable. We previously identified a cellulase, GsCelA, from thermophilic Geobacillus sp. 70PC53, which is much more thermostable than its Bacillus homolog, BsCel5A. Thus, these two cellulases provide a pair of structures ideal for investigating the mechanism regarding how these cellulases can retain activity at high temperature. In the present study, we applied the SCHEMA non-contiguous recombination algorithm as a novel tool, which assigns protein sequences into blocks for domain swapping in a way that lessens structural disruption, to generate a set of chimeric proteins derived from the recombination of GsCelA and BsCel5A. Analyzing the activity and thermostability of this designed library set, which requires only a limited number of chimeras by SCHEMA calculations, revealed that one of the blocks may contribute to the higher thermostability of GsCelA. When tested against swollen Avicel, the highly thermostable chimeric cellulase C10 containing this block showed significantly higher activity (22%-43%) and higher thermostability compared to the parental enzymes. With further structural determinations and mutagenesis analyses, a 3_(10) helix was identified as being responsible for the improved thermostability of this block. Furthermore, in the presence of ionic calcium and crown ether (CR), the chimeric C10 was found to retain 40% residual activity even after heat treatment at 90°C. Combining crystal structure determinations and structure-guided SCHEMA recombination, we have determined the mechanism responsible for the high thermostability of GsCelA, and generated a novel recombinant enzyme with significantly higher activity
Human KIT+ myeloid cells facilitate visceral metastasis by melanoma.
Metastasis of melanoma significantly worsens prognosis; thus, therapeutic interventions that prevent metastasis could improve patient outcomes. Here, we show using humanized mice that colonization of distant visceral organs with melanoma is dependent upon a human CD33+CD11b+CD117+ progenitor cell subset comprising \u3c4% of the human CD45+ leukocytes. Metastatic tumor-infiltrating CD33+ cells from patients and humanized (h)NSG-SGM3 mice showed converging transcriptional profiles. Single-cell RNA-seq analysis identified a gene signature of a KIT/CD117-expressing CD33+ subset that correlated with decreased overall survival in a TCGA melanoma cohort. Thus, human CD33+CD11b+CD117+ myeloid cells represent a novel candidate biomarker as well as a therapeutic target for metastatic melanoma
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