Q&A: What are exosomes, exactly?

Exosomes are extracellular vesicles first described as such 30 years ago and since implicated in cell-cell communication and the transmission of disease states, and explored as a means of drug discovery. Yet fundamental questions about their biology remain unanswered. Here I explore what exosomes are, highlight the difficulties in studying them and explain the current definition and some of the outstanding issues in exosome biology.Wellcome Trus

Q&A: What are exosomes, exactly?

Abstract Exosomes are extracellular vesicles first described as such 30 years ago and since implicated in cell–cell communication and the transmission of disease states, and explored as a means of drug discovery. Yet fundamental questions about their biology remain unanswered. Here I explore what exosomes are, highlight the difficulties in studying them and explain the current definition and some of the outstanding issues in exosome biology

The continuing materials analysis of the thermal control surfaces experiment (S0069)

The long term effects of the natural and induced space environment on spacecraft surfaces are critically important to future spacecraft - including Space Station Freedom. The damaging constituents of this environment include thermal vacuum, solar ultraviolet radiation, atomic oxygen, particulate radiation, and the spacecraft induced environment. The behavior of materials and coatings in the space environment continues to be a limiting technology for spacecraft and experiments. The Thermal Control Surfaces Experiment (TCSE) was flown on the National Aeronautics and Space Administration (NASA) Long Duration Exposure Facility (LDEF) to study these environmental effects on surfaces-particularly on thermal control surfaces. The TCSE was a comprehensive experiment that combined in-space measurements with extensive pre- and post-flight analyses of thermal control surfaces to determine the effects of exposure to the low Earth orbit space environment. The TCSE is the first space experiment to directly measure the total hemispherical reflectance of thermal control surfaces in the same way they are routinely measured in the laboratory. The trend analyses of selected coatings performed as part of the continuing post-flight analysis of the TCSE are described. A brief description of the TCSE and its mission on LDEF are presented. There are several publications available that describe the TCSE, it's mission on LDEF, and initial results in greater detail. These are listed in the TCSE Bibliography

Hrs- and CD63-dependent competing mechanisms make different sized endosomal intraluminal vesicles.

Multivesicular endosomes/bodies (MVBs) contain intraluminal vesicles (ILVs) that bud away from the cytoplasm. Multiple mechanisms of ILV formation have been identified, but the relationship between different populations of ILVs and MVBs remains unclear. Here, we show in HeLa cells that different ILV subpopulations can be distinguished by size. EGF stimulation promotes the formation of large ESCRT-dependent ILVs, whereas depletion of the ESCRT-0 component, Hrs, promotes the formation of a uniformly sized population of small ILVs, the formation of which requires CD63. CD63 has previously been implicated in ESCRT-independent sorting of PMEL in MVBs and transfected PMEL is present on the small ILVs that form on Hrs depletion. Upregulation of CD63-dependent ILV formation by Hrs depletion indicates that Hrs and CD63 regulate competing machineries required for the generation of distinct ILV subpopulations. Taken together our results indicate that ILV size is influenced by their cargo and mechanism of formation and suggest a competitive relationship between ESCRT-dependent and -independent mechanisms of ILV formation within single MVBs

Fluorescence of thermal control coatings on S0069 and A0114

Many of the thermal control surfaces exposed to the space environment during the 5.8 year LDEF mission experienced changes in fluorescence. All of the thermal control coatings flown on LDEF experiments S0069 and A0114 were characterized for fluorescence under ambient conditions. Some of the black coatings, having protective overcoats, appear bright yellow under ultraviolet exposure. Urethane based coatings exhibited emission spectra shifts toward longer wavelengths in the visible range. Zinc oxide pigment based coatings experienced a quenching of fluorescence, while zinc orthotitanate pigment based and other ceramic type coatings had no measurable fluorescence

ESCRTs regulate amyloid precursor protein sorting in multivesicular bodies and intracellular amyloid-β accumulation.

Intracellular amyloid-β (Aβ) accumulation is a key feature of early Alzheimer's disease and precedes the appearance of Aβ in extracellular plaques. Aβ is generated through proteolytic processing of amyloid precursor protein (APP), but the intracellular site of Aβ production is unclear. APP has been localized to multivesicular bodies (MVBs) where sorting of APP onto intraluminal vesicles (ILVs) could promote amyloidogenic processing, or reduce Aβ production or accumulation by sorting APP and processing products to lysosomes for degradation. Here, we show that APP localizes to the ILVs of a subset of MVBs that also traffic EGF receptor (EGFR), and that it is delivered to lysosomes for degradation. Depletion of the endosomal sorting complexes required for transport (ESCRT) components, Hrs (also known as Hgs) or Tsg101, inhibited targeting of APP to ILVs and the subsequent delivery to lysosomes, and led to increased intracellular Aβ accumulation. This was accompanied by dramatically decreased Aβ secretion. Thus, the early ESCRT machinery has a dual role in limiting intracellular Aβ accumulation through targeting of APP and processing products to the lysosome for degradation, and promoting Aβ secretion

Exploiting Connections for Viral Replication.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of the COVID-19 (coronavirus disease 2019) pandemic, is a positive strand RNA (+RNA) virus. Like other +RNA viruses, SARS-CoV-2 is dependent on host cell metabolic machinery to survive and replicate, remodeling cellular membranes to generate sites of viral replication. Viral RNA-containing double-membrane vesicles (DMVs) are a striking feature of +RNA viral replication and are abundant in SARS-CoV-2-infected cells. Their generation involves rewiring of host lipid metabolism, including lipid biosynthetic pathways. Viruses can also redirect lipids from host cell organelles; lipid exchange at membrane contact sites, where the membranes of adjacent organelles are in close apposition, has been implicated in the replication of several +RNA viruses. Here we review current understanding of DMV biogenesis. With a focus on the exploitation of contact site machinery by +RNA viruses to generate replication organelles, we discuss evidence that similar mechanisms support SARS-CoV-2 replication, protecting its RNA from the host cell immune response

Whisker/Cone growth on the thermal control surfaces experiment no. S0069

An unusual surface 'growth' was found during scanning electron microscope (SEM) investigations of the Thermal Control Surface Experiment (TCSE) S0069 front thermal cover. This 'growth' is similar to the cone type whisker growth phenomena as studied by G. K. Wehner beginning in the 1960's. Extensive analysis has identified the most probable composition of the whiskers to be a silicate type glass. Sources of the growth material are outgassing products from the experiment and orbital atomic oxygen, which occurs naturally at the orbital altitudes of the LDEF mission in the form of neutral atomic oxygen. The highly ordered symmetry and directionality of the whiskers are attributed to the long term (5.8 year) stable flight orientation of the LDEF

Exploiting Connections for Viral Replication.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of the COVID-19 (coronavirus disease 2019) pandemic, is a positive strand RNA (+RNA) virus. Like other +RNA viruses, SARS-CoV-2 is dependent on host cell metabolic machinery to survive and replicate, remodeling cellular membranes to generate sites of viral replication. Viral RNA-containing double-membrane vesicles (DMVs) are a striking feature of +RNA viral replication and are abundant in SARS-CoV-2-infected cells. Their generation involves rewiring of host lipid metabolism, including lipid biosynthetic pathways. Viruses can also redirect lipids from host cell organelles; lipid exchange at membrane contact sites, where the membranes of adjacent organelles are in close apposition, has been implicated in the replication of several +RNA viruses. Here we review current understanding of DMV biogenesis. With a focus on the exploitation of contact site machinery by +RNA viruses to generate replication organelles, we discuss evidence that similar mechanisms support SARS-CoV-2 replication, protecting its RNA from the host cell immune response

Probing hyperbolic polaritons using infrared attenuated total reflectance micro-spectroscopy

Hyperbolic polariton modes are highly appealing for a broad range of applications in nanophotonics, including surfaced enhanced sensing, sub-diffractional imaging and reconfigurable metasurfaces. Here we show that attenuated total reflectance micro-spectroscopy (ATR) using standard spectroscopic tools can launch hyperbolic polaritons in a Kretschmann-Raether configuration. We measure multiple hyperbolic and dielectric modes within the naturally hyperbolic material hexagonal boron nitride as a function of different isotopic enrichments and flake thickness. This overcomes the technical challenges of measurement approaches based on nanostructuring, or scattering scanning nearfield optical microscopy. Ultimately, our ATR approach allows us to compare the optical properties of small-scale materials prepared by different techniques systematicallyComment: 13 pages 4 figure