Brain 11β-Hydroxysteroid Dehydrogenase Type 1 Occupancy by Xanamem™ Assessed by PET in Alzheimer's Disease and Cognitively Normal Individuals.

Background: 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regulates intracellular cortisol and its inhibition by the small molecule inhibitor, Xanamem™, may provide a disease-modifying strategy for Alzheimer's disease (AD). Animal models suggest a range of 30-60% enzyme inhibition may suffice to provide neuroprotection.

Objective: To determine the regional brain occupancy of 11β-HSD1 by Xanamem™ in cognitively normal participants (CN) and mild cognitive impairment (MCI)/mild AD patients to investigate potential dosing ranges for future efficacy studies.

Two-Year Prognostic Utility of Plasma p217+tau across the Alzheimer's Continuum.

Background: Plasma p217+tau has shown high concordance with cerebrospinal fluid (CSF) and positron emission tomography (PET) measures of amyloid-β (Aβ) and tau in Alzheimer's Disease (AD). However, its association with longitudinal cognition and comparative performance to PET Aβ and tau in predicting cognitive decline are unknown.

Objectives: To evaluate whether p217+tau can predict the rate of cognitive decline observed over two-year average follow-up and compare this to prediction based on Aβ (18F-NAV4694) and tau (18F-MK6240) PET.

Tau, β-Amyloid, and Glucose Metabolism Following Service-Related Traumatic Brain Injury in Vietnam War Veterans: The Australian Imaging Biomarkers and Lifestyle Study of Aging-Veterans Study (AIBL-VETS).

Traumatic brain injury (TBI) is common among military veterans and has been associated with an increased risk of dementia. It is unclear if this is due to increased risk for Alzheimer's disease (AD) or other mechanisms. This case control study sought evidence for AD, as defined by the 2018 National Institute on Aging - Alzheimer's Association (NIA-AA) research framework, by measuring tau, β-amyloid, and glucose metabolism using positron emission tomography (PET) in veterans with service-related TBI.

Quantifying Inflammatory Response and Drug-Aided Resolution in an Atopic Dermatitis Model with Deep Learning.

Noninvasive quantification of dermal diseases aids efficacy studies and paves the way for broader enrollment in clinical studies across varied demographics. Related to atopic dermatitis, accurate quantification of the onset and resolution of inflammatory flare ups in the skin remains challenging because the commonly used macroscale cues do not necessarily represent the underlying inflammation at the cellular level. Although atopic dermatitis affects over 10% of Americans, the genetic underpinnings and cellular-level phenomena causing the physical manifestation of the disease require more clarity.

Visual responses in the dorsolateral frontal cortex of marmoset monkeys.

The marmoset monkey () has gained attention in neurophysiology research as a new primate model for visual processing and behavior. In particular, marmosets have a lissencephalic cortex, making multielectrode, optogenetic, and calcium-imaging techniques more accessible than other primate models. However, the degree of homology of brain circuits for visual behavior with those identified in macaques and humans is still being ascertained.

Label-Free Quantification of Pharmacokinetics in Skin with Stimulated Raman Scattering Microscopy and Deep Learning.

The treatment of inflammatory skin conditions relies on a deep understanding of how drugs and tissue behave and interact. Although numerous methods have been developed that aim to follow and quantify topical drug pharmacokinetics, these tools can come with limitations, assumptions, and trade-offs that do not allow for real-time tracking of drug flow and flux on the cellular level in situ. We have developed a quantitative imaging toolkit that makes use of stimulated Raman scattering microscopy and deep learning-based computational image analysis to quantify the uptake of specific drug molecules in skin without the need for labels.

Imaging and quantifying drug delivery in skin - Part 2: Fluorescence andvibrational spectroscopic imaging methods.

Understanding the delivery and diffusion of topically-applied drugs on human skin is of paramount importance in both pharmaceutical and cosmetics research. This information is critical in early stages of drug development and allows the identification of the most promising ingredients delivered at optimal concentrations to their target skin compartments. Different skin imaging methods, invasive and non-invasive, are available to characterize and quantify the spatiotemporal distribution of a drug within ex vivo and in vivo human skin.

Imaging and quantifying drug delivery in skin - Part 1: Autoradiography and mass spectrometry imaging.

In this two-part review we present an up-to-date description of different imaging methods available to map the localization of drugs on skin as a complement of established ex-vivo absorption studies. This first part deals with invasive methods which are grouped in two classes according to their underlying principles: i) methods using radioactivity such as autoradiography and ii) mass spectrometry methods such as MALDI and SIMS. For each method, a description of the principle is given along with example applications of imaging and quantifying drug delivery in human skin.

TIM-mediated inhibition of HIV-1 release is antagonized by Nef but potentiated by SERINC proteins.

The T cell Ig and mucin domain (TIM) proteins inhibit release of HIV-1 and other enveloped viruses by interacting with cell- and virion-associated phosphatidylserine (PS). Here, we show that the Nef proteins of HIV-1 and other lentiviruses antagonize TIM-mediated restriction. TIM-1 more potently inhibits the release of Nef-deficient relative to Nef-expressing HIV-1, and ectopic expression of Nef relieves restriction.

Nanoparticle-cell interactions induced apoptosis: a case study with nanoconjugated epidermal growth factor.

In addition to the intrinsic toxicity associated with the chemical composition of nanoparticles (NP) and their ligands, biofunctionalized NP can perturb specific cellular processes through NP-cell interactions and induce programmed cell death (apoptosis). In the case of the epidermal growth factor (EGF), nanoconjugation has been shown to enhance the apoptotic efficacy of the ligand, but the critical aspects of the underlying mechanism and its dependence on the NP morphology remain unclear. In this manuscript we characterize the apoptotic efficacy of nanoconjugated EGF as a function of NP size (with sphere diameters in the range 20-80 nm), aspect ratio (A.

Membrane Fluidity Sensing on the Single Virus Particle Level with Plasmonic Nanoparticle Transducers.

Viral membranes are nanomaterials whose fluidity depends on their composition, in particular, the cholesterol (chol) content. As differences in the membrane composition of individual virus particles can lead to different intracellular fates, biophysical tools capable of sensing the membrane fluidity on the single-virus level are required. In this manuscript, we demonstrate that fluctuations in the polarization of light scattered off gold or silver nanoparticle (NP)-labeled virus-like-particles (VLPs) encode information about the membrane fluidity of individual VLPs.

Functional Interplay Between Murine Leukemia Virus Glycogag, Serinc5, and Surface Glycoprotein Governs Virus Entry, with Opposite Effects on Gammaretroviral and Ebolavirus Glycoproteins.

Unlabelled: Gammaretroviruses, such as murine leukemia viruses (MLVs), encode, in addition to the canonical Gag, Pol, and Env proteins that will form progeny virus particles, a protein called "glycogag" (glycosylated Gag). MLV glycogag contains the entire Gag sequence plus an 88-residue N-terminal extension. It has recently been reported that glycogag, like the Nef protein of HIV-1, counteracts the antiviral effects of the cellular protein Serinc5.

Access of HIV-2 to CD169-dependent dendritic cell-mediated trans infection pathway is attenuated.

The mechanisms behind the low viral loads and lower mortality rates of HIV-2(+) individuals remain unknown. We hypothesized that reduced interaction of HIV-2 with CD169, the primary HIV-1 attachment factor on monocyte-derived dendritic cells (DCs) that targets captured virus particles to the trans infection pathway, contributes to its diminished pathogenic phenotype in vivo. We observed a significant decrease in capture of HIV-2 Gag-eGFP virus-like particles (VLPs) and infectious GFP-containing HIV-2 particles compared to corresponding HIV-1 particles by CD169(+) mature DCs.

Beneficial effects of garlic on learning and memory deficits and brain tissue damages induced by lead exposure during juvenile rat growth is comparable to the effect of ascorbic acid.

Objective: The neuroprotective effects of both garlic and ascorbic acid (AA) have been documented. In this study the effects of garlic and ascorbic acid on memory deficits and brain tissue oxidative damages induced by lead exposure was investigated.

Methods: The juvenile rats were divided and treated: (1) Control, (2) Lead (lead acetate in drinking water, 8 weeks), (3) Lead - Ascorbic Acid (Lead-AA), (4)  Lead - Garlic (100 mg/kg, daily, gavage) (Lead-Gar).

Direct current stimulation of prefrontal cortex modulates error-induced behavioral adjustments.

Commission of errors and conflict between choices might induce behavioral modulations through adjustments in the executive control of behavior and altered patterns of these modulations are detected in neuropsychiatric disorders. We examined the effects of transcranial Direct Current Stimulation (tDCS) applied over the dorsolateral prefrontal cortex (DLPFC) on error- and conflict-induced behavioral modulations. Two separate cohorts of participants performed two clinically relevant tests of executive control, respectively.

Experimental Demonstration of the Effectiveness of Electromagnetically Induced Transparency for Enhancing Cross-Phase Modulation in the Short-Pulse Regime.

We present an experiment using a sample of laser-cooled Rb atoms to show that cross-phase modulation schemes continue to benefit from electromagnetically induced transparency (EIT) even as the transparency window is made narrower than the signal bandwidth (i.e., for signal pulses much shorter than the response time of the EIT system).

Ultrahigh and persistent optical depths of cesium in Kagomé-type hollow-core photonic crystal fibers.

Alkali-filled hollow-core fibers are a promising medium for investigating light-matter interactions, especially at the single-photon level, due to the tight confinement of light and high optical depths achievable by light-induced atomic desorption (LIAD). However, until now these large optical depths could only be generated for seconds, at most once per day, severely limiting the practicality of the technology. Here we report the generation of the highest observed transient (>10(5) for up to a minute) and highest observed persistent (>2000 for hours) optical depths of alkali vapors in a light-guiding geometry to date, using a cesium-filled Kagomé-type hollow-core photonic crystal fiber (HC-PCF).

Plasmonic nanoshell functionalized etched fiber Bragg gratings for highly sensitive refractive index measurements.

A novel fiber optical refractive index sensor based on gold nanoshells immobilized on the surface of an etched single-mode fiber including a Bragg grating is demonstrated. The nanoparticle coating induces refractive index dependent waveguide losses, because of the variation of the evanescently guided part of the light. Hence the amplitude of the Bragg reflection is highly sensitive to refractive index changes of the surrounding medium.

The effect of carvacrol on systemic inflammation in guinea pigs model of COPD induced by cigarette smoke exposure.

Background: Chronic obstructive pulmonary disease (COPD) is a epidemic disease which is mainly due to cigarette smoking. The effect of carvacrol on systemic inflammation in guinea pig model of COPD was examined in the present study.

Methods: Guinea pigs of both sexes were divided into 6 groups, including: control, COPD, COPD+drinking water containing three concentrations of carvacrol and COPD+dexamethasone.

Experimental demonstration of a flexible time-domain quantum channel.

We present an experimental realization of a flexible quantum channel where the Hilbert space dimensionality can be controlled electronically. Using electro-optical modulators (EOM) and narrow-band optical filters, quantum information is encoded and decoded in the temporal degrees of freedom of photons from a long-coherence-time single-photon source. Our results demonstrate the feasibility of a generic scheme for encoding and transmitting multidimensional quantum information over the existing fiber-optical telecommunications infrastructure.

Quantifying lipid contents in enveloped virus particles with plasmonic nanoparticles.

Phosphatidylserine (PS) and monosialotetrahexosylganglioside (GM1 ) are examples of two host-derived lipids in the membrane of enveloped virus particles that are known to contribute to virus attachment, uptake, and ultimately dissemination. A quantitative characterization of their contribution to the functionality of the virus requires information about their relative concentrations in the viral membrane. Here, a gold nanoparticle (NP) binding assay for probing relative PS and GM1 lipid concentrations in the outer leaflet of different HIV-1 and Ebola virus-like particles (VLPs) using sample sizes of less than 3 × 10(6) particles is introduced.

Adipose-derived stromal cell therapy affects lung inflammation and tracheal responsiveness in guinea pig model of COPD.

The effects of adipose derived stromal cells (ASCs) were evaluated on tracheal responsiveness and biochemical parameters in guinea pigs model of chronic obstructive pulmonary disease (COPD). Thirty six guinea pigs were divided into 6 groups including: Control, COPD, COPD+intratracheal delivery of PBS (COPD+ITPBS), COPD+intravenous delivery of PBS (COPD+IVPBS), COPD+intratracheal delivery of ASCs (COPD+ITASC) and COPD+intravenous injection of ASCs (COPD+IVASC). COPD was induced by exposing animals to cigarette smoke for 3 months.