Sex-driven variability in TSPO-expressing microglia in MS patients and healthy individuals

Background: Males with multiple sclerosis (MS) have a higher risk for disability progression than females, but the reasons for this are unclear.Objective: We hypothesized that potential differences in TSPO-expressing microglia between female and male MS patients could contribute to sex differences in clinical disease progression.Methods: The study cohort consisted of 102 MS patients (mean (SD) age 45.3 (9.7) years, median (IQR) disease duration 12.1 (7.0–17.2) years, 72% females, 74% relapsing–remitting MS) and 76 age- and sex-matched healthy controls. TSPO-expressing microglia were measured using the TSPO-binding radioligand [11C](R)-PK11195 and brain positron emission tomography (PET). TSPO-binding was quantified as distribution volume ratio (DVR) in normal-appearing white matter (NAWM), thalamus, whole brain and cortical gray matter (cGM).Results: Male MS patients had higher DVRs compared to female patients in the whole brain [1.22 (0.04) vs. 1.20 (0.02), p = 0.002], NAWM [1.24 (0.06) vs. 1.21 (0.05), p = 0.006], thalamus [1.37 (0.08) vs. 1.32 (0.02), p = 0.008] and cGM [1.25 (0.04) vs. 1.23 (0.04), p = 0.028]. Similarly, healthy men had higher DVRs compared to healthy women except for cGM. Of the studied subgroups, secondary progressive male MS patients had the highest DVRs in all regions, while female controls had the lowest DVRs.Conclusion: We observed higher TSPO-binding in males compared to females among people with MS and in healthy individuals. This sex-driven inherent variability in TSPO-expressing microglia may predispose male MS patients to greater likelihood of disease progression.<br/

Ubiquitin sets the timer: impacts on aging and longevity

Protein homeostasis is essential for cellular function, organismal growth and viability. Damaged and aggregated proteins are turned over by two major proteolytic routes of the cellular quality-control pathways: the ubiquitin-proteasome system and autophagy. For both these pathways, ubiquitination provides the recognition signal for substrate selection. This Commentary discusses how ubiquitin-dependent proteolytic pathways are coordinated with stress- and aging-induced signals

Insights into disseminated MS brain pathology with multimodal diffusion tensor and PET imaging

Objective To evaluate in vivo the co-occurrence of microglial activation and microstructural white matter (WM) damage in the MS brain and to examine their association with clinical disability.Methods 18-kDa translocator protein (TSPO) brain PET imaging was performed for evaluation of microglial activation by using the radioligand [11C](R)-PK11195. TSPO binding was evaluated as the distribution volume ratio (DVR) from dynamic PET images. Diffusion tensor imaging (DTI) and conventional MRI (cMRI) were performed at the same time. Mean fractional anisotropy (FA) and mean (MD), axial, and radial (RD) diffusivities were calculated within the whole normal-appearing WM (NAWM) and segmented NAWM regions appearing normal in cMRI. Fifty-five patients with MS and 15 healthy controls (HCs) were examined.Results Microstructural damage was observed in the NAWM of the MS brain. DTI parameters of patients with MS were significantly altered in the NAWM compared with an age- and sex-matched HC group: mean FA was decreased, and MD and RD were increased. These structural abnormalities correlated with increased TSPO binding in the whole NAWM and in the temporal NAWM (p Conclusions Widespread structural disruption in the NAWM is linked to neuroinflammation, and both phenomena associate with clinical disability. Multimodal PET and DTI allow in vivo evaluation of widespread MS pathology not visible using cMRI.</div

Observations of the luminous red nova AT 2021biy in the nearby galaxy NGC 4631

We present an observational study of the luminous red nova (LRN) AT\,2021biy in the nearby galaxy NGC\,4631. The field of the object was routinely imaged during the pre-eruptive stage by synoptic surveys, but the transient was detected only at a few epochs from $\sim 231$\,days before maximum brightness. The LRN outburst was monitored with unprecedented cadence both photometrically and spectroscopically. AT\,2021biy shows a short-duration blue peak, with a bolometric luminosity of $\sim 1.6 \times 10^{41}$\,erg\,s$^{-1}$, followed by the longest plateau among LRNe to date, with a duration of 210\,days. A late-time hump in the light curve was also observed, possibly produced by a shell-shell collision. AT\,2021biy exhibits the typical spectral evolution of LRNe. Early-time spectra are characterised by a blue continuum and prominent H emission lines. Then, the continuum becomes redder, resembling that of a K-type star with a forest of metal absorption lines during the plateau phase. Finally, late-time spectra show a very red continuum ($T_{\mathrm{BB}} \approx 2050$ K) with molecular features (e.g., TiO) resembling those of M-type stars. Spectropolarimetric analysis indicates that AT\,2021biy has local dust properties similar to those of V838\,Mon in the Milky Way Galaxy. Inspection of archival {\it Hubble Space Telescope} data taken on 2003 August 3 reveals a $\sim 20$\,\msun\ progenitor candidate with log\,$(L/{\rm L}_{\odot}) = 5.0$\,dex and $T_{\rm{eff}} = 5900$\,K at solar metallicity. The above luminosity and colour match those of a luminous yellow supergiant. Most likely, this source is a close binary, with a 17--24\,\msun\ primary component.Comment: 21 pages, 14 figures. Accepted by Astronomy and Astrophysic

Forbidden hugs in pandemic times III. Observations of the luminous red nova AT 2021biy in the nearby galaxy NGC 4631

We present an observational study of the luminous red nova (LRN) AT 2021biy in the nearby galaxy NGC 4631. The field of the object was routinely imaged during the pre-eruptive stage by synoptic surveys, but the transient was detected only at a few epochs from ∼231 days before maximum brightness. The LRN outburst was monitored with unprecedented cadence both photometrically and spectroscopically. AT 2021biy shows a short-duration blue peak, with a bolometric luminosity of ∼1.6 × 1041 erg s−1, followed by the longest plateau among LRNe to date, with a duration of 210 days. A late-time hump in the light curve was also observed, possibly produced by a shell-shell collision. AT 2021biy exhibits the typical spectral evolution of LRNe. Early-time spectra are characterised by a blue continuum and prominent H emission lines. Then, the continuum becomes redder, resembling that of a K-type star with a forest of metal absorption lines during the plateau phase. Finally, late-time spectra show a very red continuum (TBB ≈ 2050 K) with molecular features (e.g., TiO) resembling those of M-type stars. Spectropolarimetric analysis indicates that AT 2021biy has local dust properties similar to those of V838 Mon in the Milky Way Galaxy. Inspection of archival Hubble Space Telescope data taken on 2003 August 3 reveals a ∼20 M⊙ progenitor candidate with log (L/L⊙) = 5.0 dex and Teff = 5900 K at solar metallicity. The above luminosity and colour match those of a luminous yellow supergiant. Most likely, this source is a close binary, with a 17–24 M⊙ primary component. </p

OUHANDS database for hand detection and pose recognition

Abstract In this paper we propose a publicly available static hand pose database called OUHANDS and protocols for training and evaluating hand pose classification and hand detection methods. A comparison between the OUHANDS database and existing databases is given. Baseline results for both of the protocols are presented

Dimethyl fumarate decreases short-term but not long-term inflammation in a focal EAE model of neuroinflammation

Background Dimethyl fumarate (DMF) is an oral immunomodulatory drug used in the treatment of autoimmune diseases. Here, we sought to study whether the effect of DMF can be detected using positron emission tomography (PET) targeting the 18-kDa translocator protein (TSPO) in the focal delayed-type hypersensitivity rat model of multiple sclerosis (fDTH-EAE). The rats were treated orally twice daily from lesion activation (day 0) with either vehicle (tap water with 0.08% Methocel, 200 mu L; control group n = 4 (3 after week four)) or 15 mg/kg DMF (n = 4) in 0.08% aqueous Methocel (200 mu L) for 8 weeks. The animals were imaged by PET using the TSPO tracer [F-18]GE-180 in weeks 0, 1, 2, 4, 8, and 18 following lesion activation, and the non-displaceable binding potential (BPND) was calculated. Immunohistochemical staining for Iba1, CD4, and CD8 was performed in week 18, and in separate cohorts of animals, following 2 or 4 weeks of treatment. Results Using the fDTH-EAE model, DMF reduced the [F-18]GE-180 BPND in the DMF-treated animals compared to control animals after 1 week of treatment (two-tailed unpaired t test, p = 0.031), but not in weeks 2, 4, 8, or 18 when imaged in vivo by PET. Immunostaining for Iba1 showed that DMF had no effect on the perilesional volume or the core lesion volume after 2 or 4 weeks of treatment, or at 18 weeks. However, the optical density (OD) measurements of CD4(+) staining showed reduced OD in the lesions of the treated rats. Conclusions DMF reduced the microglial activation in the fDTH-EAE model after 1 week of treatment, as detected by PET imaging of the TSPO ligand [F-18]GE-180. However, over an extended time course, reduced microglial activation was not observed using [F-18]GE-180 or by immunohistochemistry for Iba1(+) microglia/macrophages. Additionally, DMF did affect the infiltration of CD4(+) and CD8(+) T-lymphocytes at the fDTH-EAE lesion.</p