MicroRNA profiling reveals marker of motor neuron disease in ALS models

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder marked by the loss of motor neurons (MNs) in the brain and spinal cord, leading to fatally debilitating weakness. Because this disease predominantly affects MNs, we aimed to characterize the distinct expression profile of that cell type to elucidate underlying disease mechanisms and to identify novel targets that inform on MN health during ALS disease time course. microRNAs (miRNAs) are short, noncoding RNAs that can shape the expression profile of a cell and thus often exhibit cell-type-enriched expression. To determine MN-enriched miRNA expression, we used Cre recombinase-dependent miRNA tagging and affinity purification in mice. By defining thein vivomiRNA expression of MNs, all neurons, astrocytes, and microglia, we then focused on MN-enriched miRNAs via a comparative analysis and found that they may functionally distinguish MNs postnatally from other spinal neurons. Characterizing the levels of the MN-enriched miRNAs in CSF harvested from ALS models of MN disease demonstrated that one miRNA (miR-218) tracked with MN loss and was responsive to an ALS therapy in rodent models. Therefore, we have used cellular expression profiling tools to define the distinct miRNA expression of MNs, which is likely to enrich future studies of MN disease. This approach enabled the development of a novel, drug-responsive marker of MN disease in ALS rodents.SIGNIFICANCE STATEMENTAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease in which motor neurons (MNs) in the brain and spinal cord are selectively lost. To develop tools to aid in our understanding of the distinct expression profiles of MNs and, ultimately, to monitor MN disease progression, we identified small regulatory microRNAs (miRNAs) that were highly enriched or exclusive in MNs. The signal for one of these MN-enriched miRNAs is detectable in spinal tap biofluid from an ALS rat model, where its levels change as disease progresses, suggesting that it may be a clinically useful marker of disease status. Furthermore, rats treated with ALS therapy have restored expression of this MN RNA marker, making it an MN-specific and drug-responsive marker for ALS rodents.</jats:p

Early JWST imaging reveals strong optical and NIR color gradients in galaxies at z∼2z\sim2 driven mostly by dust

Recent studies have shown that galaxies at cosmic noon are redder in the center and bluer in the outskirts, mirroring results in the local universe. These color gradients could be caused by either gradients in the stellar age or dust opacity; however, distinguishing between these two causes is impossible with rest-frame optical photometry alone. Here we investigate the underlying causes of the gradients from spatially-resolved rest-frame $U-V$ vs. $V-J$ color-color diagrams, measured from early observations with the James Webb Space Telescope. We use $1\, \mu m - 4\, \mu m$ NIRCam photometry from the CEERS survey of a sample of 54 galaxies with $M_* / M_\odot>10$ at redshifts $1.7<z<2.3$ selected from the 3D-HST catalog. We model the light profiles in the F115W, F200W and F356W NIRCam bands using \texttt{imcascade}, a Bayesian implementation of the Multi-Gaussian expansion (MGE) technique which flexibly represents galaxy profiles using a series of Gaussians. We construct resolved rest-frame $U-V$ and $V-J$ color profiles. The majority of star-forming galaxies have negative gradients (i.e. redder in the center, bluer in the outskirts) in both $U-V$ and $V-J$ colors consistent with radially decreasing dust attenuation. A smaller population (roughly 15\%) of star-forming galaxies have positive $U-V$ but negative $V-J$ gradients implying centrally concentrated star-formation. For quiescent galaxies we find a diversity of UVJ color profiles, with roughly one-third showing star-formation in their center. This study showcases the potential of JWST to study the resolved stellar populations of galaxies at cosmic noon.Comment: Updated to match published version, new Figure 5 and some text change

Planning for Project ECHO in New Hampshire

Assuring a healthy New Hampshire requires making sure that all of the state’s residents can get the right care in the right place at the right time. Yet, access to timely, effective health care is not always a given in our state, especially for vulnerable populations. Health and community care workforce shortages, long distances to care, and social, economic, and cultural barriers make accessing care challenging for many. The Project ECHO Model™ is an evidence-based method using web-based teleconferencing to link specialist teams with community-based sites to help community providers improve their ability to manage complex conditions. It has been proven to improve health care outcomes for vulnerable populations with limited access to care because of socioeconomic factors or geography. The New Hampshire Project ECHO® (Extension for Community Healthcare Outcomes) Planning for Implementation and Business Sustainability Project (Planning for Project ECHO in NH) undertook a planning process to inform how to best to develop Project ECHO at UNH to serve New Hampshire health and community care providers and ultimately improve access to effective, timely care. Planning for Project ECHO in NH also developed a business and sustainability plan for long-term success of the UNH Project ECHO Hub and an evaluation plan for measuring efficacy. Planning for Project ECHO in NH included: A Project ECHO Needs Assessment and Prioritization Process, including review of existing needs assessments in the field; a stakeholder survey of health and community care providers conducted by the New Hampshire Citizens Health Initiative (Initiative); and analysis of data from the NH Comprehensive Health Information System (NH CHIS), NH’s all-payer claims database (APCD). A business and sustainability plan including Key Informant Interviews, an environmental scan, and a template for business sustainability planning to identify funding sources and structures to sustain Project ECHO in NH. A framework for Project ECHO evaluation

The Impact of Sociodemographic Factors, Comorbidities and Physiologic Response on 30-day Mortality in COVID-19 Patients in Metropolitan Detroit

BACKGROUND: The relationship of health disparities and comorbidities in coronavirus disease 2019 (COVID-19) related outcomes are an ongoing area of interest. This report assesses risk factors associated with mortality in patients presenting with Covid-19 infection and healthcare disparities. METHODS: A retrospective cohort study of consecutive patients presenting to emergency departments within an integrated health system who tested positive for COVID-19 between March 7 and April 30, 2020 in Metropolitan Detroit. The primary outcomes were hospitalization and 30-day mortality. RESULTS: A total of 3,633 patients with mean age of 58 years were included. The majority were female and black non-Hispanic. Sixty-four percent required hospitalization, 56% of whom were black. Hospitalized patients were older, more likely to reside in a low-income area, and had a higher burden of comorbidities. By 30-days, 433 (18.7%) hospitalized patients died. In adjusted analyses, the presence of comorbidities, age \u3e60 years and more severe physiological disturbance were associated with 30-day mortality. Residence in low income areas (odds ratio, 1.02; 95% confidence interval 0.76 - 1.36), and public insurance (odds ratio, 1.24; 95% confidence interval 0.76 - 2.01) were not independently associated with higher risk of mortality. Black female patients had a lower adjusted risk of mortality (odds ratio, 0.46; 95% confidence interval, 0.27 to 0.78). CONCLUSIONS: In this large cohort of COVID-19 patients, those with comorbidities, advanced age, and physiological abnormalities on presentation had higher odds of death. Disparities in income or source of health insurance were not associated with outcomes. Black women had a lower risk of dying

Remarkably Compact Quiescent Candidates at 3<z<53<z<5 in JWST-CEERS

In this letter, we measure the rest-frame optical and near-infrared sizes of ten quiescent candidates at $3<z<5$, first reported by Carnall et al. (2023a). We use James Webb Space Telescope (JWST) Near-Infrared Camera (NIRCam) F277W and F444W imaging obtained through the public CEERS Early Release Science (ERS) program and imcascade, an astronomical fitting code that utilizes Multi-Gaussian Expansion, to carry out our size measurements. When compared to the extrapolation of rest-optical size-mass relations for quiescent galaxies at lower redshift, eight out of ten candidates in our sample (80%) are on average more compact by $\sim$40%. Seven out of ten candidates (70%) exhibit rest-frame infrared sizes $\sim$10% smaller than rest-frame optical sizes, indicative of negative color gradients. Two candidates (20%) have rest-frame infrared sizes $\sim$1.4$\times$ larger than rest-frame optical sizes; one of these candidates exhibits signs of ongoing or residual star formation, suggesting this galaxy may not be fully quenched. The remaining candidate is unresolved in both filters, which may indicate an Active Galactic Nuclei (AGN). Strikingly, we observe three of the most massive galaxies in the sample (log(M$_{\star}$/M$_{\odot}$) = 10.74 - 10.95) are extremely compact, with effective radii ${\sim}$0.7 kpc. Our findings provide no indication that the size evolution relation flattens out, and may indicate that the size evolution of quiescent galaxies is steeper than previously anticipated beyond $z>3$.Comment: Accepted for publication in ApJL. 11 pages, 4 figures, 1 tabl

Rest-Frame Near-Infrared Radial Light Profiles up to z=3 from JWST/NIRCam: Wavelength Dependence of the S\'ersic Index

We examine the wavelength dependence of radial light profiles based on S\'ersic index $n$ measurements of 1067 galaxies with M$_*\geq$ 10$^{9.5}$M$_\odot$ and in the redshift range $0.5 < z < 3$. The sample and rest-frame optical light profiles are drawn from CANDELS$+$3D-HST; rest-frame near-infrared light profiles are inferred from CEERS JWST/NIRCam imaging. $n$ shows only weak dependence on wavelength, regardless of redshift, galaxy mass and type: on average, star-forming galaxies have $n = 1-1.5$ and quiescent galaxies have $n = 3-4$ in the rest-frame optical and near-infrared. The strong correlation at all wavelengths between $n$ and star-formation activity implies a physical connection between the radial stellar mass profile and star-formation activity. The main caveat is that the current sample is too small to discern trends for the most massive galaxies (M$_* > 10^{11}M_\odot$).Comment: 15 pages, 7 figures, Submitted to ApJ. Comments welcom

Rest-frame near-infrared sizes of galaxies at cosmic noon: objects in JWST's mirror are smaller than they appeared

Galaxy sizes and their evolution over cosmic time have been studied for decades and serve as key tests of galaxy formation models. However, at $z\gtrsim1$ these studies have been limited by a lack of deep, high-resolution rest-frame infrared imaging that accurately traces galaxy stellar mass distributions. Here, we leverage the new capabilities of the James Webb Space Telescope to measure the 4.4$\mu$m sizes of ${\sim}1000$ galaxies with $\log{\rm{M}_*/\rm{M}_\odot}\ge9$ and $1.0\le z \le 2.5$ from public CEERS imaging in the EGS deep field. We compare the sizes of galaxies measured from NIRCam imaging at 4.4$\mu$m ($\lambda_{\mathrm{rest}}\sim1.6\mu$m) with sizes measured at $1.5\mu$m ($\lambda_{\mathrm{rest}}\sim5500$A). We find that, on average, galaxy half-light radii are $\sim8$% smaller at 4.4$\mu$m than 1.5$\mu$m in this sample. This size difference is markedly stronger at higher stellar masses and redder rest-frame $V-J$ colors: galaxies with ${\rm M}_* \sim 10^{11}\,{\rm M}_\odot$ have 4.4$\mu$m sizes that are $\sim 25$% smaller than their 1.5$\mu$m sizes. Our results indicate that galaxy mass profiles are significantly more compact than their rest-frame optical light profiles at cosmic noon, and demonstrate that spatial variations in age and attenuation are important, particularly for massive galaxies. The trend that we find here impacts our understanding of the size growth and evolution of galaxies, and suggests that previous studies based on rest-frame optical light may not have captured the mass-weighted structural evolution of galaxies. This paper represents a first step towards a new understanding of the morphologies of early massive galaxies enabled by JWST's infrared window into the distant universe.Comment: Accepted to ApJL. 10 pages, 4 figures, 1 table with full size catalog in F150W and F444