African swine fever virus is a complex double-stranded DNA virus that exhibits tropism for cells of the mononuclear phagocytic system. Virus replication is a multi-step process that involves the nucleus of the host cell as well the formation of large perinuclear sites where progeny virions are assembled prior to transport to, and budding through, the plasma membrane. Like many viruses, African swine fever virus reorganises the cellular architecture to facilitate its replication and has evolved multiple mechanisms to avoid the potential deleterious effects of host cell stress response pathways.
View Article and Find Full Text PDFAlopecia areata (AA) is an autoimmune disease that affects approximately 2% of the general population. Patients with AA most commonly present with one or more patches of hair loss on the scalp in defined circular areas. A fraction of patients progress to more severe forms of the disease, in some cases with involvement of all body surfaces.
View Article and Find Full Text PDFAfrican swine fever virus multigene family (MGF) 360 and 505 genes have roles in suppressing the type I interferon response and in virulence in pigs. The role of the individual genes is poorly understood. Different combinations of these genes were deleted from the virulent genotype II Georgia 2007/1 isolate.
View Article and Find Full Text PDFLactoferrin is a glycoprotein found at high concentrations within exocrine secretions, including tears. Low levels of lactoferrin have been implicated in the loss of tear secretion and ageing. Furthermore, lactoferrin possesses a range of functionalities, including anti-inflammatory properties and the ability to modulate the gut microbiota.
View Article and Find Full Text PDFPathogen transmission from wildlife hosts to genetically distinct species is a major driver of disease emergence. African swine fever virus (ASFV) persists in sub-Saharan Africa through a sylvatic cycle between warthogs and soft ticks that infest their burrows. The virus does not cause disease in these animals, however transmission of the virus to domestic pigs or wild boar causes a hemorrhagic fever that is invariably fatal.
View Article and Find Full Text PDFBullous pemphigoid (BP) is an autoantibody-mediated blistering disease that is often associated with neurologic disease. BP antibodies target two epidermal adhesion molecules, known as BP180 and BP230. Homologues to these proteins are found in the brain, and it is hypothesized that neurologic disease leads to the production of autoantibodies that can cross-react with their cutaneous forms.
View Article and Find Full Text PDFIn the original publication, abstract text, one of the co-author's name and the legend to Table 1 were incorrectly published.
View Article and Find Full Text PDFPurpose: To evaluate the efficacy and safety of autologous serum (AS) eye drops combined with punctal plugs (PPs) in patients with Sjögren syndrome (SS)-related dry eye.
Methods: A retrospective clinical study was performed in patients with dry eye caused by SS. We evaluated the Schirmer test value, tear breakup time (tBUT), and fluorescein and Rose Bengal (RB) staining scores at baseline, 3 months, 6 months, 1 year, and >1 year after treatment.
During apoptosis, mitochondrial outer membrane permeabilization (MOMP) is often a point-of-no-return; death can proceed even if caspase activation is disrupted. However, under certain conditions, resistance to MOMP-dependent, caspase-independent cell death is observed. Mitochondrial recovery represents a key process in this survival.
View Article and Find Full Text PDFCaspase-2 is an initiator caspase activated in response to heat shock and other stressors that induce apoptosis. Activation of caspase-2 requires induced proximity resulting after recruitment to caspase-2 activation complexes such as the PIDDosome. We have adapted bimolecular fluorescence complementation (BiFC) to measure caspase-2 induced proximity in real time in single cells.
View Article and Find Full Text PDFLive cell imaging allows several key apoptotic events to be visualized in a single cell over time. These include mitochondrial outer membrane permeabilization (MOMP), mitochondrial dysfunction, phosphatidylserine exposure, and membrane permeabilization. Here we describe a protocol for imaging multiple apoptotic processes in the same cell over time.
View Article and Find Full Text PDFIt was previously reported that the ciliary epithelium (CE) of the mammalian eye contains a rare population of cells that could produce clonogenic self-renewing pigmented spheres in culture. Based on their ability to up-regulate genes found in retinal neurons, it was concluded that these sphere-forming cells were retinal stem cells. This conclusion raised the possibility that CE-derived retinal stem cells could help to restore vision in the millions of people worldwide who suffer from blindness associated with retinal degeneration.
View Article and Find Full Text PDFLysosomal exocytosis is a Ca2+-regulated mechanism that involves proteins responsible for cytoskeletal attachment and fusion of lysosomes with the plasma membrane. However, whether luminal lysosomal enzymes contribute to this process remains unknown. Here we show that neuraminidase NEU1 negatively regulates lysosomal exocytosis in hematopoietic cells by processing the sialic acids on the lysosomal membrane protein LAMP-1.
View Article and Find Full Text PDFThe use of live cell microscopy has made a number of contributions to the study of apoptosis. Many of the tools and techniques are available that allow us to image the key events that occur during cell death including mitochondrial outer membrane permeabilization, mitochondrial transmembrane potential changes, translocation of Bcl-2 family members, caspase activation, phosphatidylserine flip and plasma membrane rupture. We discuss these techniques here and highlight the advantages and drawbacks of using such approaches to study apoptosis.
View Article and Find Full Text PDFPhagocytosis and autophagy are two ancient, highly conserved processes involved, respectively, in the removal of extracellular organisms and the destruction of organisms in the cytosol. Autophagy, for either metabolic regulation or defence, involves the formation of a double membrane called the autophagosome, which then fuses with lysosomes to degrade the contents, a process that has similarities with phagosome maturation. Toll-like-receptor (TLR) engagement activates a variety of defence mechanisms within phagocytes, including facilitation of phagosome maturation, and also engages autophagy.
View Article and Find Full Text PDFalpha(4)beta(1) and alpha(4)beta(7) integrins are key regulators of physiologic and pathologic responses in inflammation and autoimmune disease. The effectiveness of anti-integrin antibodies to attenuate a number of inflammatory/immune conditions provides a strong rationale to target integrins for drug development. Important advances have been made in identifying potent and selective candidates, peptides and peptidomimetics, for further development.
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