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1 compared to naturally secreted exosomes (SEC-exosomes).
2 on, inflammatory response, and extracellular exosome.
3 hich encodes a structural subunit of the RNA exosome.
4          PROMPTs are degraded by the nuclear exosome.
5 es BMMO HuR expression and its transfer into exosome.
6 s partly attenuated through ILK knockdown in exosomes.
7 mbly, but it is not itself incorporated into exosomes.
8 patients, MTEX accounted for 23-66% of total exosomes.
9 ese membrane scaffolds for the production of exosomes.
10 bearing a specific sequence (EXO motif) into exosomes.
11 c and neuronal functions and are reported in exosomes.
12 intercellular communication when secreted as exosomes.
13 by increasing secretory miR-23c level in the exosomes.
14 lpha-synuclein and syntenin-1) from neuronal exosomes.
15 heir activation leads to robust secretion of exosomes.
16 hosphorylation in cells, and associated with exosomes.
17 e and precise isolation of subpopulations of exosomes.
18 anding both autocrine and paracrine roles of exosomes.
19  the sorting and delivery of tetraspanins to exosomes.
20  enhances peripheral insulin sensitivity via exosomes.
21 gh release of extracellular vesicles such as exosomes.
22 port, and analysis of electroactive drugs in exosomes.
23 ed exosomal protein biomarkers of the target exosomes.
24 ty in a paracrine manner through circulating exosomes.
25 hich having masses in the range expected for exosomes.
26 cluding immune cells, can secrete and uptake exosomes.
27 y be specific to microvesicles as opposed to exosomes.
28 organelles generate the final content of the exosomes.
29 nal and hypothalamic peptides in addition to exosomes.
30 NA profiling was performed on plasma-derived exosomes.
31 irm that these samples have been enriched in exosomes.
32 nt a method for stimulating the secretion of exosomes.
33                                 ILK-enriched exosomes activated NF-kappaB (nuclear factor kappaB) pat
34  an exosome core component, or components of exosome adaptor complexes, we identify ~2900 transcripti
35 ifying Cproteins in plasma astrocyte-derived exosomes (ADEs) of subjects with sports-related TBI (sTB
36          Small extracellular vesicles called exosomes affect multiple autocrine and paracrine cellula
37 ble to selectively recover cancer-associated exosomes, allowing for important insights into patient d
38 etry analysis revealed wild-type EPC-derived exosome and IL-10 knockout EPC-derived exosome contain d
39 lar nanoporation produced up to 50-fold more exosomes and a more than 10(3)-fold increase in exosomal
40 on of sEVs corresponding to both traditional exosomes and a novel subset of vesicles containing both
41 uch fusions can be detected in tumor-derived exosomes and could potentially represent an early detect
42 DNs was enriched for those that bind to VCaP exosomes and discriminate them from exosomes derived fro
43 ng analytical efforts to separate and purify exosomes and exosome subpopulations.
44 Moreover, miR-26a is down-regulated in serum exosomes and islets of obese mice.
45   In addition, extracellular vesicles (EVs), exosomes and microvesicles, containing cargo mediators,
46 zing the physical and chemical properties of exosomes and other EVs.
47 n clearance by preventing it release through exosomes and promoting lysosomal degradation of misfolde
48 all extracellular vesicles (sEVs), including exosomes and small microvesicles, represent an understud
49 ship between expression of IRS-1 in L1CAM(+) exosomes and systemic IR as assessed by homeostatic mode
50 ive to combine the targeting capabilities of exosomes and the bio-orthogonal potential of Pd nanopart
51 rthermore, we discuss the role of lncRNAs in exosomes and their function in drug resistance, and ther
52                        Viruses can spread in exosomes and thereby avoid immune recognition(3).
53 and their subpopulations (micro-vesicles and exosomes), and microRNAs (miRNA-21-3p, miRNA-150-5p, and
54 as small molecules, proteins, nanoparticles, exosomes, and amyloid fibrils.
55 o be enriched in astrocytes and secreted via exosomes, and antipsychotics were shown to control its c
56 including microRNA, circulating tumor cells, exosomes, and cell-free DNA, and discuss the opportunity
57 R4 was required for the protective effect of exosomes, and exosomal HSP70 interacted with TLR4 on hai
58 ial repair by upregulating ILK enrichment in exosomes, and ILK-mediated activation of NF-kappaB pathw
59 ed proteolytically by BACE1, is released via exosomes, and is a potent diffusible inhibitor of regene
60 ery using M1 macrophages, macrophage-derived exosomes, and macrophage-membrane-coated nanoparticles a
61 s mainly in the size range closer to that of exosomes, and that the average alpha-syn concentrations
62 onfirms the notion that mRNA products of the exosome are direct substrates for DcpS.
63                                              Exosomes are also a promising class of novel drug delive
64                                              Exosomes are attractive as nucleic-acid carriers because
65                                              Exosomes are cell-secreted microvesicles that play impor
66                                              Exosomes are emerging as new regulators of intercellular
67                                    Plasmatic exosomes are extracellular vesicles involved in the inte
68                              Human milk (HM) exosomes are highly enriched in microRNAs (miRNAs), whic
69                                              Exosomes are highly enriched in tetraspanins (TSPNs) and
70                                              Exosomes are lipid bilayer-enclosed EVs of 30-150 nm in
71                                              Exosomes are nanosized (30-150 nm) extracellular vesicle
72                                              Exosomes are naturally derived 50-150 nm nanovesicles th
73   Although the protein constituents of these exosomes are often glycosylated, a large-scale character
74                     The identified genes and exosomes are potential therapeutic targets for stopping
75 secretion, and uptake of immune cell-derived exosomes are regulated by intracellular proteins and ext
76                                              Exosomes are secreted extracellular vesicles carrying di
77                                              Exosomes are small EVs with growing recognition for thei
78                                              Exosomes are small extracellular vesicles involved in ma
79  Cellular nanoporation may enable the use of exosomes as a universal nucleic-acid carrier for applica
80 essed the clinical utility of serum neuronal exosomes as biomarkers across the spectrum of Parkinson'
81 1 carries its cargo, at most, to the site of exosome assembly, but it is not itself incorporated into
82         Here, we show that both standard and exosome-associated preparations of AAV8 vectors can effe
83 in recipient cells, whereas ILK knockdown in exosomes attenuates NF-kappaB activation and reduces inf
84  target kinase for improving progenitor cell exosome-based cardiac therapies.
85 w that caveolin-1 (Cav1) centrally regulates exosome biogenesis and exosomal protein cargo sorting th
86  multiprotein ESCRT complex participating in exosome biogenesis.
87 gnore whether these work together to control exosome biology.
88 multiplex characterizations of NSCLC-derived exosomes by bioaffinity interactions of antibodies and d
89 his work, we intend to isolate and visualize exosomes by combining an affinity-based method and passi
90 th dissipation monitoring (QCM-D), to detect exosomes by exploiting their surface protein profile.
91 from a triblock copolymer which encapsulates exosomes by polymeric self-assembly and maintains their
92 ells is increased relative to late endosomal exosomes by reducing growth regulatory Akt/mechanistic T
93                Mechanistically, secretion of exosomes by these spheres was essential for enhancing su
94 protein, and have shown that PDL1-expressing exosomes can inhibit antitumour immune responses.
95                          Immune cell-derived exosomes can mediate crosstalk between innate and adapti
96 d to investigate if modification of specific exosome cargo can rescue reparative activity.
97  miRNAs and FMR1, play a significant role in exosome cargo loading and enhanced secretion during cell
98 trical stimulus that promotes the release of exosomes carrying transcribed mRNAs and targeting peptid
99 d from fly to human, is described here, with exosomes carrying unique cargos, including the GTPase Ra
100      The limitations and scarcity of current exosome characterization approaches have led to a growin
101 alcium leads to release of chelation-induced exosomes (CI-exosomes) from OVCAR-3 EOC cells.
102                         Schwann cell-derived exosomes communicate with dorsal root ganglia (DRG) neur
103         Yet, little is known about how these exosomes compare to those that are continuously released
104 selectively process or degrade RNAs, the RNA exosome complex dictates the levels of RNAs comprising m
105 our analysis to different mutants of the RNA exosome complex, we explore how substrate channeling thr
106 cleolyticly shortened from the 3' end by the exosome complex.
107 s emphasize the potential value of different exosome components in distinguishing between healthy, pr
108 G198D mutation prevents binding to other RNA exosome components, resulting in protein and complex ins
109 stic analyses have demonstrated that the RNA exosome confers expression of a differentiation regulato
110  identified a significant proportion of host exosome constituents.
111 rived exosome and IL-10 knockout EPC-derived exosome contain different protein expression pattern.
112                        HIV-associated saliva exosomes contain the HIV trans-activation response eleme
113 ith human alpha-synuclein preformed fibrils, exosomes containing alpha-synuclein released by microgli
114 d C2BBe1 and intestinal organoids to secrete exosomes containing viral components and have the abilit
115                The TAR RNA in HIV-associated exosomes contributes to enhancing KSHV infectivity throu
116                Cell-to-cell communication by exosomes controls normal and pathogenic processes(1,2).
117                              By depleting an exosome core component, or components of exosome adaptor
118                           Still, the nuclear exosome could have protein-coding (pc) gene-specific reg
119 nce in the field suggests that tumor-derived exosomes could be responsible for mediating systemic imm
120 PTs are sources of small interfering RNAs in exosome-deficient mutants, perhaps explaining why plants
121 or tumor-stroma interactions through a novel exosome-dependent ECM deposition mechanism.
122                                              Exosomes derived from both hDPSCs and MDPCs upregulated
123  tested with human serum samples spiked with exosomes derived from healthy human serum and a prostate
124 study investigated the therapeutic effect of exosomes derived from healthy Schwann cells (SC-Exos) on
125  to VCaP exosomes and discriminate them from exosomes derived from LNCaP prostate cancer cells.
126                             By this way, the exosomes derived from normal lung and NSCLC cells can be
127        Image analysis of fluorescent labeled exosomes derived from three cell lines injected systemic
128      Furthermore, compared to the OVX group, exosomes, derived from the loading group, promoted the a
129        There is a growing need for cancerous exosome detection towards potential non-invasive cancer
130 lectrochemical and electrical biosensors for exosomes detection in the field of cancer and other dise
131                                           CI-exosomes display a unique miRNA profile compared to natu
132 rends, challenges and future perspectives of exosome-driven POCT in liquid biopsy have been discussed
133 IL-10 (interleukin-10) deficient-EPC-derived exosome dysfunction in myocardial repair and to investig
134                   Plasma endothelial-derived exosomes (EDEs) were enriched by two-step immunoabsorpti
135 s of the protein and RNA content of captured exosomes enable further molecular analysis of exosomes,
136 antibody against EGFR, blocks HIV-associated exosome-enhanced KSHV infection.
137 ogy and herein report an increased number of exosomes enriched for L1CAM, a marker predominantly expr
138 hat an inhalation treatment of secretome and exosome exhibited therapeutic potential for lung regener
139                                              Exosomes, extracellular vesicles (EVs) of endosomal orig
140 alpha-toxin through the release of ADAM10 on exosomes-extracellular vesicles of endosomal origin.
141 glycan microheterogeneity within the urinary exosomes, finding on average 5.9 glycans per site.
142  nanomedicine including CRISPR nanoparticle, exosomes for the treatment of BC/TNBC and other molecula
143 ize-based subpopulations (e.g., exomeres and exosomes) for further analysis.
144                                 An alternate exosome formation mechanism, which is conserved from fly
145 rane scaffolds appreciated for their role in exosome formation, composition, and activity, we current
146                          Herein, we identify exosomes from autologous breast cancer cells that show e
147  of 1) rapid isolation and identification of exosomes from both malignant and healthy cells and 2) mu
148                                              Exosomes from cancer cells have great potential to be ap
149                    Release of Rab11-positive exosomes from cancer cells is increased relative to late
150 sential step in the formation and release of exosomes from cells that is critical for intracellular c
151                                     Monocyte exosomes from coinfected persons increased in microRNA (
152     Transplantation of splenocytes and serum exosomes from elafin-overexpressing HFD-treated donor mi
153 ggested that miR-16 and miR-148a enriched in exosomes from FAK-null CAFs contribute to the reduced tu
154                                     Isolated exosomes from heat-shocked utricles were sufficient to i
155 ression profiles in first week postpartum HM exosomes from HIV-1 infected and uninfected control moth
156 G DNA induce the secretion of ADAM10-bearing exosomes from human cells as well as in mice.
157                                              Exosomes from IAA/DNP-treated or untreated cells had sim
158  underlying mechanism of loss of function of exosomes from inflamed EPCs is still obscure.
159                                              Exosomes from macrophages exposed to diabetic milieu (hi
160           After long-term exposure to inject exosomes from MKN-45 cells, mice developed an immunosupp
161 n size and shape to previously characterized exosomes from other organisms and that these EVs contain
162 neomycin, whereas inhibition or depletion of exosomes from the extracellular environment abolished th
163        The composition of ESCRT complexes in exosomes from VCaP versus LNCaP cells might constitute a
164 to release of chelation-induced exosomes (CI-exosomes) from OVCAR-3 EOC cells.
165 0 deficiency/inflammation alters EPC-derived exosome function, content and therapeutic effect on myoc
166 r showed that FAK ablation in CAFs decreased exosome functions to promote tumor cell migration and ot
167  microglial proinflammatory cytokines, these exosomes further increased protein aggregation in neuron
168 er in vivo studies showed that CBSA/siS100A4@Exosome had a higher affinity toward lung in comparison
169 own whether diabetic milieu affects cellular/exosome-HuR and its implications on cardiac inflammation
170 talytically active subunit Rrp44/Dis3 of the exosome in budding yeast (Saccharomyces cerevisiae) is c
171       However, the role of beta-cell-derived exosomes in metabolic homeostasis is poorly understood.
172 ay between the immune system and circulating exosomes in metastatic breast cancer (MBC).
173          Furthermore, addition of astrocytic exosomes in neuronal cultures resulted in a significant
174 able alternative method for the detection of exosomes in scarce resource settings.
175 lin receptor substrate-1 (IRS-1) in L1CAM(+) exosomes in subjects with MDD as compared with age- and
176 y, by purifying microglia/macrophage derived exosomes in the CSF of Parkinson's disease patients, we
177 s initial study, we describe the analysis of exosomes in the serum of healthy subjects, intraductal p
178 xosomes enable further molecular analysis of exosomes, including Western blot and quantitative polyme
179 enous tumor exosomal PD-L1 and tumor-derived exosome-induced PD-L1 are two of the most notable mechan
180                            The biogenesis of exosomes involves their origin in endosomes, and subsequ
181                                      The RNA exosome is a multisubunit protein complex involved in RN
182                                      The RNA exosome is an essential ribonuclease complex required fo
183 reveal that saliva containing HIV-associated exosomes is a risk factor for the enhancement of KSHV in
184      Accurate biological characterization of exosomes is an important step toward clinical applicatio
185  uncoating of HAV particles contained in the exosomes, is mainly responsible for exo-HAV infectivity
186 s sites developed after mice were exposed to exosomes isolated from all three gastric cancer cell lin
187 was demonstrated by stereotaxic injection of exosomes isolated from alpha-synuclein preformed fibrils
188 the tumor environment was investigated using exosomes isolated from gastric cancer cell lines MKN-28,
189                                    Moreover, exosomes isolated from the muscle of trained mice displa
190 tracellular vesicles (sEVs, formerly termed "exosomes") isolated at ~100 000g are known, a wide range
191      Furthermore, treatment with CI- and SEC-exosomes leads to differential biophysical and functiona
192  fluorescent tag allows visualization of the exosome lifecycle, including multivesicular body (MVB) t
193 KD2 and PKHD1 genes, are abundant in urinary exosome-like vesicles (ELVs) where they form the polycys
194 g lung spheroid cell-secretome (LSC-Sec) and exosomes (LSC-Exo) by inhalation to treat different mode
195             The capsid-free viral RNA in the exosome lumen, but not the endosomal uncoating of HAV pa
196 mon membrane origin, and utilization of host exosome machinery for virion assembly and egress.
197                                         CD81 exosome marker-normalized ADE levels of classical pathwa
198 agentless impedimetric assay of two internal exosome markers (alpha-synuclein and syntenin-1) from ne
199 es that carry HSP70 in addition to canonical exosome markers and other proteins.
200       GSDMD and IL-1beta colocalize with the exosome markers CD63 and ALIX intracellularly, and GSDMD
201                            Among traditional exosome markers, CD9, HSPA8, ALIX, and HSP90AB1 represen
202 and containing a defined set of constitutive exosome markers.
203                  Hence, immune cell-secreted exosomes may have applications in cancer diagnosis and i
204 ding of how inflammation may alter stem cell-exosome-mediated cardiac repair and identifies ILK as a
205 ects on breast cancer cell migration through exosome-mediated delivery.
206 L1 are two of the most notable mechanisms of exosome-mediated resistance against antitumor immunity a
207 C4-membrane attack complex and ROS regulates exosome-mediated, ethanol-induced beta-endorphin neurona
208 vation and gene expression, monocyte-derived exosome micro-ribonucleic acid (miRNA) expression, plasm
209            Extracellular vesicles, including exosomes/microvesicles (EMVs), have been described as se
210 new insights into how gastric cancer derived exosomes modulate the immune response to promote lung tu
211 re into two fractions: melanoma cell-derived exosomes (MTEX) and normal cell-derived exosomes (non-MT
212  able to reach a limit of detection of 10(5) exosomes muL(-1) directly in human serum, when performin
213 ived exosomes (MTEX) and normal cell-derived exosomes (non-MTEX).
214      (8)) participate in cargo delivery from exosomes of hepatitis A virus (HAV)-infected cells (exo-
215 evealed that miR-214-3p was increased in the exosomes of the bone-losing ovariectomized (OVX) mice, w
216  used to introduce a therapeutic load inside exosomes often involve disruption of their membrane, whi
217  In this study, the impact of tumor secreted exosomes on immune function in the tumor environment was
218  endothelial progenitor cell (EPC) and their exosomes on myocardial repair, although the underlying m
219 odies and then used to immobilize and enrich exosomes on their surfaces using antigen-antibody affini
220 rent forms of extracellular PDL1, such as on exosomes or as a freely soluble protein, and have shown
221            Tumor cells secrete PD-L1 through exosomes or splice variants, which has been described as
222 erive either from the endosomal compartment (exosomes) or as a result of shedding from the plasma mem
223                            Inhibition of the exosome pathway decreased EV-A71 replication and release
224        Therefore, we establish that the host exosome pathway is intrinsic for HCMV maturation, and re
225 ediated by previously unreported pDC-derived exosomes (pDCexos), that were also produced by pDCs unde
226                          We characterized an exosome population averaging 100 +/- 50 nm in diameter a
227 ental factors contribute to heterogeneity in exosome populations and how different exosome population
228 ity in exosome populations and how different exosome populations mediate diversity in stromal cell be
229 ess of alpha-synuclein in neuronally derived exosomes predates the clinical presentation of Parkinson
230 ystemically into C57BL/6 mice revealed these exosomes primarily localize to the lungs.
231 urther, qRT-PCR analysis with the same serum exosomes processed for EXO-NGS, we observed two long non
232                     (ii) The accumulation of exosomes produced by cells in which the gene encoding hn
233           Melanoma patients' plasma contains exosomes produced by malignant and normal cells.
234          (i) hnRNPA2B1 is not a component of exosomes produced in HEp-2 or HEK293T cells.
235 we show that hnRNPA2B1 is not a component of exosomes produced in HEp-2 or HEK293T cells.
236 Compared with bulk electroporation and other exosome-production strategies, cellular nanoporation pro
237                                  Transferred exosomes protect host cells in vitro by serving as scave
238 ndings underpin future investigation of host exosome proteins as important modulators of HCMV replica
239                 Thus, we selected a panel of exosome proteins for knock down, and confirmed that loss
240                          We demonstrate that exosomes purified from the saliva of HIV-positive patien
241 ngle bead for an accurate fluorescence-based exosome quantification.
242                                              Exosomes reflect heterogeneous biological changes associ
243 crease of brain nSMase2 activity and related exosome release have been implicated in various patholog
244 nvestigated the roles of Rab27a, a player in exosome release, and TRAF3IP2, an inflammatory mediator,
245 on to infectious microvesicles, CD9-positive exosomes released from PV-infected cells are also infect
246  validate this acquisition, we characterized exosomes released from uninfected cells, and demonstrate
247 erived, breast and pancreatic cancer-derived exosomes, respectively, when the correct aptamer sequenc
248 ficient glioma mouse models, mRNA-containing exosomes restored tumour-suppressor function, enhanced i
249        The controlled release of odontogenic exosomes resulted in a reparative dentin bridge formatio
250 lumenal vesicles at endosomes (the source of exosomes) revealed general and domain-specific effects o
251 g speckle association correlate with reduced exosome RNA degradation and larger Ser2p CTD-modified RN
252 miRNA profile compared to naturally secreted exosomes (SEC-exosomes).
253 ale) subjects, we uncovered that miR-223, an exosome-secreted miRNA that targets glutamate receptors,
254   However, little is known about the role of exosome-secreted miRNAs in the regulation of glutamate r
255                                              Exosome secretion by cells is a complex, poorly understo
256 ological synapse and plays a crucial role in exosome secretion.
257 ts, even from cells with low basal levels of exosome secretion.
258 c and resulted in a 3 to 16-fold increase in exosome secretion.
259                                CBSA/siS100A4@Exosome self-assembled nanoparticles formed homogeneous
260 or genes are overrepresented among loci with exosome-sensitive antisense RNAs, suggesting a potential
261 e active TSSs, alternative TSSs that produce exosome-sensitive transcripts typically do not contribut
262 tes (TSSs) from within pc genes that produce exosome-sensitive transcripts.
263           Lastly, profiling of miRs from CAF exosomes showed alterations of several exosomal miRs in
264  ILK knockdown in IL-10 knockout EPC-derived exosome significantly rescued their reparative dysfuncti
265 ly depends on cell communication mediated by exosomes, small vesicles generated within multivesicular
266  efforts to separate and purify exosomes and exosome subpopulations.
267 ings expand the number of genes encoding RNA exosome subunits linked to human disease while also sugg
268 tor (NgR1)-interacting Nogo-66 domain on the exosome surface.
269 persed element-1 family, through the nuclear exosome targeting-mediated nuclear degradation.
270 -infected cells can secrete HCV RNA carrying exosomes that can infect cells in a receptor independent
271 se to heat stress, inner ear tissue releases exosomes that carry HSP70 in addition to canonical exoso
272 se to infection, facilitating the release of exosomes that serve as decoys for bacterially produced t
273  release small extracellular vesicles (sEVs, exosomes) that contain lipids and proteins, RNA, and DNA
274                     The unique biogenesis of exosomes, their ubiquitous production by all cell types,
275 defective in nuclear RNA decay including the exosome to reassess the existence of Arabidopsis PROMPTs
276 ty of small secretory microvesicles known as exosomes to influence neuronal and glial function via th
277  is a Rab27b effector protein with a role in exosome transport and is encoded by the EXPH5 gene.
278 xO1 is decreased in the liver of trained and exosome-treated mice.
279 rization, whereas IL-10 knockout EPC-derived exosome treatment showed diminished and opposite effects
280 rdial infarction (MI), wild-type EPC-derived exosome treatment significantly improved left ventricle
281                Protection was independent of exosomes under the conditions tested.
282 esicular body (MVB) trafficking, MVB fusion, exosome uptake and endosome acidification.
283  protein FMR1 and directs miRNA loading into exosomes via interaction with components of the ESCRT (e
284            The in vivo significance of these exosomes was demonstrated by stereotaxic injection of ex
285 llular vesicle (EV) preparation enriched for exosomes were directly determined for the first time by
286                                              Exosomes were efficiently extracted from patient sera us
287 egulatory proteins in MTEX, non-MTEX and HDs exosomes were evaluated by on-bead flow cytometry.
288                       In this design, target exosomes were firstly captured by latex beads via aldimi
289       The increased IRS-1 levels in L1CAM(+) exosomes were greater in subjects with MDD and were asso
290                                       Plasma exosomes were isolated and separated by immunocapture in
291                                              Exosomes were isolated from plasma by ExoQuick solution
292                            We further showed exosomes were mainly taken up by natural killer cells an
293  are transported in body fluids often within exosomes, which are small cell-derived vesicles that fun
294  controlled, tunable release of cell-derived exosomes, which maintains their advantageous physiologic
295 esence of alpha-synuclein oligomer in CD11b+ exosomes, which were able to induce alpha-synuclein aggr
296 imulates release from Rab11a compartments of exosomes with pro-tumorigenic functions, which we propos
297                                Functionally, exosomes with the Nogo-66 domain on their surface potent
298                                              Exosomes, with an average diameter of ~100 nanometers, a
299                             Although the RNA exosome would be expected to control diverse biological
300                                   Studies of exosomes would be facilitated by a method for increasing

 
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