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| 2. |
- Cereda, Maurizio, et al.
(författare)
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Imaging the Injured Lung : Mechanisms of Action and Clinical Use
- 2019
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Ingår i: Anesthesiology. - : LIPPINCOTT WILLIAMS & WILKINS. - 0003-3022 .- 1528-1175. ; 131:3, s. 716-749
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Forskningsöversikt (refereegranskat)abstract
- Acute respiratory distress syndrome (ARDS) consists of acute hypoxemic respiratory failure characterized by massive and heterogeneously distributed loss of lung aeration caused by diffuse inflammation and edema present in interstitial and alveolar spaces. It is defined by consensus criteria, which include diffuse infiltrates on chest imaging-either plain radiography or computed tomography. This review will summarize how imaging sciences can inform modern respiratory management of ARDS and continue to increase the understanding of the acutely injured lung. This review also describes newer imaging methodologies that are likely to inform future clinical decision-making and potentially improve outcome. For each imaging modality, this review systematically describes the underlying principles, technology involved, measurements obtained, insights gained by the technique, emerging approaches, limitations, and future developments. Finally, integrated approaches are considered whereby multimodal imaging may impact management of ARDS.
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| 3. |
- Holland, Linda Z, et al.
(författare)
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The amphioxus genome illuminates vertebrate origins and cephalochordate biology
- 2008
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 18:7, s. 1100-1111
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Tidskriftsartikel (refereegranskat)abstract
- Cephalochordates, urochordates, and vertebrates evolved from a common ancestor over 520 million years ago. To improve our understanding of chordate evolution and the origin of vertebrates, we intensively searched for particular genes, gene families, and conserved noncoding elements in the sequenced genome of the cephalochordate Branchiostoma floridae, commonly called amphioxus or lancelets. Special attention was given to homeobox genes, opsin genes, genes involved in neural crest development, nuclear receptor genes, genes encoding components of the endocrine and immune systems, and conserved cis-regulatory enhancers. The amphioxus genome contains a basic set of chordate genes involved in development and cell signaling, including a fifteenth Hox gene. This set includes many genes that were co-opted in vertebrates for new roles in neural crest development and adaptive immunity. However, where amphioxus has a single gene, vertebrates often have two, three, or four paralogs derived from two whole-genome duplication events. In addition, several transcriptional enhancers are conserved between amphioxus and vertebrates--a very wide phylogenetic distance. In contrast, urochordate genomes have lost many genes, including a diversity of homeobox families and genes involved in steroid hormone function. The amphioxus genome also exhibits derived features, including duplications of opsins and genes proposed to function in innate immunity and endocrine systems. Our results indicate that the amphioxus genome is elemental to an understanding of the biology and evolution of nonchordate deuterostomes, invertebrate chordates, and vertebrates.
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| 4. |
- Johansson, Erik, et al.
(författare)
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Nuclear receptor TLX inhibits TGF-beta signaling in glioblastoma
- 2016
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Ingår i: Experimental Cell Research. - : Elsevier BV. - 0014-4827. ; 343:2, s. 118-125
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Tidskriftsartikel (refereegranskat)abstract
- TLX (also called NR2E1) is an orphan nuclear receptor that maintains sternness of neuronal stem cells. TLX is highly expressed in the most malignant form of glioma, glioblastoma multiforme (GBM), and is important for the proliferation and maintenance of the stem/progenitor cells of the tumor. Transforming Growth Factor-beta (TGF-beta) is a cytokine regulating many different cellular processes such as differentiation, migration, adhesion, cell death and proliferation. TGF-beta has an important function in cancer where it can work as either a tumor suppressor or oncogene, depending on the cancer type and stage of tumor development. Since glioblastoma often have dysfunctional TGF-beta signaling we wanted to find out if there is any interaction between TLX and TGF-beta in glioblastoma cells. We demonstrate that knockdown of TLX enhances the canonical TGF-beta signaling response in glioblastoma cell lines. TLX physically interacts with and stabilizes Smurf1, which can ubiquitinate and target TGF-beta receptor II for degradation, whereas knockdown of TLX leads to stabilization of TGF-beta receptor II, increased nuclear translocation of Smad2/3 and enhanced expression of TGF-beta target genes. The interaction between TLX and TGF-beta may play an important role in the regulation of proliferation and tumor-initiating properties of glioblastoma cells.
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| 5. |
- Kamiie, Junichi, et al.
(författare)
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Amyloid-specific extraction using organic solvents
- 2020
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Ingår i: MethodsX. - : Elsevier BV. - 2215-0161. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Typing of amyloidosis by mass spectrometry (MS) based proteomic analysis contribute to the diagnosis of amyloidosis. For MS analysis, laser microdissection (LMD) is used for amyloid specific sampling. This study aimed to establish a method for selectively extracting amyloids from formalin-fixed, paraffin-embedded (FFPE) specimens by organic solvent instead of LMD. The extracts using dimethyl sulfoxide (DMSO), dimethylformamide (DMF), methanol, trifluoroethanol (TFE) or hexafluoro-2-propanol from FFPE brain of alzheimer's disease mouse model generated protein bands on SDS-PAGE, and Aβ was identified in the extract of DMF using mass spectrometry. The extract using DMSO from the kidney of a AA amyloidosis patient produced a protein band in SDS-PAGE. This protein band was identified to be serum amyloid A (SAA) by Western blotting and mass spectrometry. Circular dichroism spectrometry revealed that the secondary structures of Aβ and transthyretin were converted to α-helices from β-sheets in TFE. Our results suggest that organic solvents can extract amyloids from FFPE specimens by converting their secondary structure. This method could eliminate the LMD step and simplified amyloid typing by MS analysis. • DMSO, DMF, methanol, TFE and HFIP can extract Aβ specifically from the FFPE brain of a Alzheimer’ disease mouse model. • DMSO can extract SAA specifically from a FFPE section of AA amyloidosis. • Secondary structures of Aβ and transthyretin converted from β-sheet to α-helix in TFE.
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| 6. |
- Koga, Shigehiro, et al.
(författare)
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In vivo subcellular imaging of tumors in mouse models using a fluorophore-conjugated anti-carcinoembryonic antigen antibody in two-photon excitation microscopy
- 2014
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Ingår i: Cancer Science. - : Wiley. - 1347-9032 .- 1349-7006. ; 105:10, s. 1299-1306
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Tidskriftsartikel (refereegranskat)abstract
- Recently, there has been growing interest in applying fluorescence imaging techniques to the study of various disease processes and complex biological phenomena in vivo. To apply these methods to clinical settings, several groups have developed protocols for fluorescence imaging using antibodies against tumor markers conjugated to fluorescent substances. Although these probes have been useful in macroscopic imaging, the specificity and sensitivity of these methods must be improved to enable them to detect micro-lesions in the early phases of cancer, resulting in better treatment outcomes. To establish a sensitive and highly specific imaging method, we used a fluorophore-conjugated anti-carcinoembryonic antigen (CEA) antibody to perform macroscopic and microscopic in vivo imaging of inoculated cancer cells expressing GFP with or without CEA. Macroscopic imaging by fluorescence zoom microscopy revealed that bio-conjugation of Alexa Fluor 594 to the anti-CEA antibody allowed visualization of tumor mass consisting of CEA-expressing human cancer cells, but the background levels were unacceptably high. In contrast, microscopic imaging using a two-photon excitation microscope and the same fluorescent antibody resulted in subcellular-resolution imaging that was more specific and sensitive than conventional imaging using a fluorescence zoom microscope. These results suggest that two-photon excitation microscopy in conjunction with fluorophore-conjugated antibodies could be widely adapted to detection of cancer-specific cell-surface molecules, both in cancer research and in clinical applications.
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| 7. |
- Morais, Caio C. A., et al.
(författare)
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High Positive End-Expiratory Pressure Renders Spontaneous Effort Noninjurious
- 2018
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - : AMER THORACIC SOC. - 1073-449X .- 1535-4970. ; 197:10, s. 1285-1296
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: In acute respiratory distress syndrome (ARDS), atelectatic solid-like lung tissue impairs transmission of negative swings in pleural pressure (Ppl) that result from diaphragmatic contraction. The localization of more negative Ppl proportionally increases dependent lung stretch by drawing gas either from other lung regions (e.g., nondependent lung [pendelluft]) or from the ventilator. Lowering the level of spontaneous effort and/or converting solid-like to fluid-like lung might render spontaneous effort noninjurious.Objectives: To determine whether spontaneous effort increases dependent lung injury, and whether such injury would be reduced by recruiting atelectatic solid-like lung with positive end-expiratory pressure (PEEP).Methods: Established models of severe ARDS (rabbit, pig) were used. Regional histology (rabbit), inflammation (positron emission tomography; pig), regional inspiratory Ppl (intrabronchial balloon manometry), and stretch (electrical impedance tomography; pig) were measured. Respiratory drive was evaluated in 11 patients with ARDS.Measurements and Main Results: Although injury during muscle paralysis was predominantly in nondependent and middle lung regions at low (vs. high) PEEP, strong inspiratory effort increased injury (indicated by positron emission tomography and histology) in dependent lung. Stronger effort (vs. muscle paralysis) caused local overstretch and greater tidal recruitment in dependent lung, where more negative Ppl was localized and greater stretch was generated. In contrast, high PEEP minimized lung injury by more uniformly distributing negative Ppl, and lowering the magnitude of spontaneous effort (i.e., deflection in esophageal pressure observed in rabbits, pigs, and patients).Conclusions: Strong effort increased dependent lung injury, where higher local lung stress and stretch was generated; effort-dependent lung injury was minimized by high PEEP in severe ARDS, which may offset need for paralysis.
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| 8. |
- Morokuma, Tomoki, et al.
(författare)
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OISTER optical and near-infrared monitoring observations of peculiar radio-loud active galactic nucleus SDSSJ110006.07+442144.3
- 2017
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Ingår i: Nippon Tenmon Gakkai obun kenkyu hokoku. - : Oxford University Press (OUP). - 0004-6264. ; 69:5
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Tidskriftsartikel (refereegranskat)abstract
- We present monitoring campaign observations at optical and near-infrared (NIR) wavelengths for a radio-loud active galactic nucleus (AGN) at z = 0.840, SDSSJ110006.07+442144.3 (hereafter, J1100+4421), which was identified during a flare phase in late 2014 February. The campaigns consist of three intensive observing runs from the discovery to 2015 March, mostly within the scheme of the OISTER collaboration. Optical-NIR light curves and simultaneous spectral energy distributions (SEDs) are obtained. Our measurements show the strongest brightening in 2015 March. We found that the optical-NIR SEDs of J1100+4421 show an almost steady shape despite the large and rapid intranight variability. This constant SED shape is confirmed to extend to similar to 5 mu m in the observed frame using the archival WISE data. Given the lack of absorption lines and the steep power-law spectrum of alpha(upsilon) similar to -1.4, where f(v) proportional to v(alpha upsilon), synchrotron radiation by a relativistic jet with no or small contributions from the host galaxy and the accretion disk seemsmost plausible as an optical-NIR emission mechanism. The steep optical-NIR spectral shape and the large amplitude of variability are consistent with this object being a low.peak jet-dominated AGN. In addition, sub-arcsecond resolution optical imaging data taken with Subaru Hyper Suprime-Cam does not show a clear extended component and the spatial scales are significantly smaller than the large extensions detected at radio wavelengths. The optical spectrum of a possible faint companion galaxy does not show any emission lines at the same redshift, and hence a merging hypothesis for this AGN-related activity is not supported by our observations.
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| 9. |
- Zeng, Zhao-jun, et al.
(författare)
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TLX controls angiogenesis through interaction with the von Hippel-Lindau protein.
- 2012
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Ingår i: Biology open. - : The Company of Biologists. - 2046-6390. ; 1:6, s. 527-35
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Tidskriftsartikel (refereegranskat)abstract
- TLX is known as the orphan nuclear receptor indispensable for maintaining neural stem cells in adult neurogenesis. We report here that neuroblastoma cell lines express high levels of TLX, which further increase in hypoxia to enhance the angiogenic capacity of these cells. The proangiogenetic activity of TLX appears to be induced by its direct binding to the von Hippel-Lindau protein (pVHL), which stabilizes TLX. In turn, TLX competes with hydroxylated hypoxia-inducible factor (HIF-α) for binding to pVHL, which contributes to the stabilization of HIF-2α in neuroblastoma during normoxia. Upon hypoxia, TLX increases in the nucleus where it binds in close proximity of the HIF-response element on the VEGF-promoter chromatin, and, together with HIF-2α, recruits RNA polymerase II to induce VEGF expression. Conversely, depletion of TLX by shRNA decreases the expression of HIF-2α and VEGF as well as the growth-promoting and colony-forming capacity of the neuroblastoma cell lines IMR-32 and SH-SY5Y. On the contrary, silencing HIF-2α will slightly increase TLX, suggesting that TLX acts to maintain a hypoxic environment when HIF-2α is decreasing. Our results demonstrate TLX to play a key role in controlling angiogenesis by regulating HIF-2α. TLX and pVHL might counterbalance each other in important fate decisions such as self-renewal and differentiation, as well as angiogenesis and anti-angiogenesis.
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