High-resolution, multiplexed experiments are a staple in cellular imaging. Analogous experiments in animals are challenging, however, due to substantial scattering and autofluorescence in tissue at ...visible (350-700 nm) and near-infrared (700-1,000 nm) wavelengths. Here, we enable real-time, non-invasive multicolour imaging experiments in animals through the design of optical contrast agents for the shortwave infrared (SWIR, 1,000-2,000 nm) region and complementary advances in imaging technologies. We developed tunable, SWIR-emissive flavylium polymethine dyes and established relationships between structure and photophysical properties for this class of bright SWIR contrast agents. In parallel, we designed an imaging system with variable near-infrared/SWIR excitation and single-channel detection, facilitating video-rate multicolour SWIR imaging for optically guided surgery and imaging of awake and moving mice with multiplexed detection. Optimized dyes matched to 980 nm and 1,064 nm lasers, combined with the clinically approved indocyanine green, enabled real-time, three-colour imaging with high temporal and spatial resolutions.
Optical imaging within the shortwave infrared (SWIR, 1000–2000 nm) region of the electromagnetic spectrum has enabled high-resolution and high-contrast imaging in mice, non-invasively. Polymethine ...dyes, with their narrow absorption spectra and high absorption coefficients, are optimal probes for fast and multiplexed SWIR imaging. Here, we expand upon the multiplexing capabilities in SWIR imaging by obtaining brighter polymethine dyes with varied excitation wavelengths spaced throughout the near-infrared (700–1000 nm) region. Building on the flavylium polymethine dye scaffold, we explored derivatives with functional group substitution at the 2-position, deemed chromenylium polymethine dyes. The reported dyes have reduced nonradiative rates and enhanced emissive properties, enabling non-invasive imaging in mice in a single color at 300 fps and in three colors at 100 fps. Combined with polymethine dyes containing a red-shifted julolidine flavylium heterocycle and indocyanine green, distinct channels with well-separated excitation wavelengths provide non-invasive video-rate in vivo imaging in four colors.
As an emergent developmental construct, derailment – an individual difference hallmarked by a temporal discordance of the self – has been positively associated with depressive features, though less ...is known about the role of stress in this relationship. The aim of the present study was to explore the interaction between derailment and subjective stress on depressed mood.
265 adults recruited through Prolific – a crowd sourcing platform were first tasked with completing baseline measures, then were randomly assigned to a low stress or high stress condition. We utilized an adapted version of the Online Trier Stress Test to manipulate stress levels. Next, depressed mood and post-test perceived stress were measured. We analyzed data through STATA using a two-tailed independent samples t-test and multiple linear regression.
Findings suggested the experimental manipulation increased subjective stress within the high stress condition compared to the low stress condition (Mdiff = 36.14, SE = 4.4, t = 8.21, p < .001). Further, we found the interaction between derailment and stress conditions was associated with increased depressed mood (β = −0.11, SE = 0.05, p = .038, R2 = 0.5). Notably, we found significant between-condition differences in depressed mood for those who endorsed either low (d = 0.22, SE = 0.07, p = .003) or moderate levels of derailment (d = 0.11, SE = 0.05, p = .033), but not for those who endorsed high levels of derailment (d = 0.01, SE = 0.07, p = .92).
This study utilized self-report measures, which may be susceptible to biased responses.
Derailment may play a role in the persistence of depressed mood regardless of varying contexts of stress.
•We focus on the role of derailment in the relationship between levels of subjective stress and depressed mood.•Contrary to our hypothesis, derailment negatively moderated this relationship.•We found significant differences in depressed mood at different levels of derailment only within the low stress condition.•The present study is the first to experimentally explore the impact of derailment and subjective stress on depressed mood.
High resolution, multiplexed experiments are a staple in cellular imaging. Analogous experiments in animals are challenging, however, due to significant scattering and autofluorescence in tissue at ...visible (VIS, 350–700 nm) and near-infrared (NIR, 700–1000 nm) wavelengths. Here, we enable real-time, non-invasive multicolor imaging experiments in animals through the design of optical contrast agents for the shortwave infrared (SWIR, 1000–2000 nm) region and complementary advances in imaging technologies. We developed tunable, SWIR-emissive flavylium polymethine dyes and established structure-photophysical property relationships for this class of bright SWIR contrast agents. In parallel, we designed an imaging system with variable NIR/SWIR excitation and single-channel detection, facilitating video-rate multicolor SWIR imaging for optically guided surgery and imaging of awake and moving mice with multiplexed detection. Optimized dyes matched to 980 nm and 1064 nm lasers, combined with the clinically approved indocyanine green, enabled real-time, three-color imaging with high temporal and spatial resolutions.
Human immunodeficiency virus type-1 (HIV-1) particles incorporate a trimeric envelope complex (Env) made of gp120 (SU) and gp41 (TM) heterodimers. It has been previously established that soluble CD4 ...(sCD4) interaction leads to shedding of gp120 from viral particles, and that gp120 may also be easily lost from virions during incubation or particle purification procedures. In the design of HIV particle or pseudovirion-based HIV vaccines, it may be important to develop strategies to maximize the gp120 content of particles. We analyzed the gp120 retention of HIV-1 laboratory-adapted isolates and primary isolates following incubation with sCD4 and variations in temperature. NL4-3 shed gp120 readily in a temperature- and sCD4-dependent manner. Surprisingly, inactivation of the viral protease led to markedly reduced shedding of gp120. Gp120 shedding was shown to vary markedly between HIV-1 strains, and was not strictly determined by whether the isolate was adapted to growth on immortalized T cell lines or was a primary isolate. Pseudovirions produced by expression of codon-optimized
gag and
env genes also demonstrated enhanced gp120 retention when an immature core structure was maintained. Pseudovirions of optimal stability were produced through a combination of an immature Gag protein core and a primary isolate Env. These results support the feasibility of utilizing pseudovirion particles as immunogens for the induction of humoral responses directed against native envelope structures.
Reports of intraarterial papaverine infusion as treatment for cerebral vasospasm are few and documented complications are uncommon. The authors report the case of a patient with paradoxical ...aggravation of cerebral arterial narrowing during selective intraarterial papaverine infusion intended to treat vasospasm following aneurysmal subarachnoid hemorrhage (SAH). A 48-year-old man presented to the authors' service with symptomatic vasospasm 10 days after experiencing an SAH. The ruptured anterior communicating artery aneurysm was surgically obliterated the following day, and thereafter maximum hypervolemic and hypertensive therapies were used. However, the patient remained lethargic, and a stable xenon-computerized tomography (CT) cerebral blood flow (CBF) study revealed CBF to be 15 cc/100 g/minute in the left anterior cerebral artery (ACA) and 25 cc/100 g/minute in the right ACA territories. Cerebral arteriography demonstrated diffuse severe left ACA and mild left middle cerebral artery (MCA) vasospasm. In response intraarterial papaverine was infused into the internal carotid artery just proximal to the ophthalmic artery. During the infusion the patient became aphasic and exhibited right hemiplegia. Arteriography performed immediately after the intraarterial papaverine infusion revealed diffuse exacerbation of vasospasm in the distal ACA and MCA territories. A repeat xenon-CT CBF study showed that CBF in the left ACA and the MCA had drastically decreased (2 cc/100 g/minute and 10 cc/100 g/minute, respectively). Despite aggressive management, infarction ultimately developed. This is the first clinical case to illustrate a paradoxical effect of intraarterial papaverine treatment for vasospasm following aneurysmal SAH. The possible mechanisms of this paradoxical response and potential therapeutic reactions are reviewed.
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