Tracing Galaxy Formation with Stellar Halos I: Methods

If the favored hierarchical cosmological model is correct, then the Milky Way system should have accreted ~100-200 luminous satellite galaxies in the past \~12 Gyr. We model this process using a hybrid semi-analytic plus N-body approach which distinguishes explicitly between the evolution of light and dark matter in accreted satellites. This distinction is essential to our ability to produce a realistic stellar halo, with mass and density profile much like that of our own Galaxy, and a surviving satellite population that matches the observed number counts and structural parameter distributions of the satellite galaxies of the Milky Way. Our model stellar halos have density profiles which typically drop off with radius faster than those of the dark matter. They are assembled from the inside out, with the majority of mass (~80%) coming from the \~15 most massive accretion events. The satellites that contribute to the stellar halo have median accretion times of ~9 Gyr in the past, while surviving satellite systems have median accretion times of ~5 Gyr in the past. This implies that stars associated with the inner halo should be quite different chemically from stars in surviving satellites and also from stars in the outer halo or those liberated in recent disruption events. We briefly discuss the expected spatial structure and phase space structure for halos formed in this manner. Searches for this type of structure offer a direct test of whether cosmology is indeed hierarchical on small scales.Comment: 22 pages, 16 figures, submitted to Ap

β-Amyloid promotes accumulation of lipid peroxides by inhibiting CD36-mediated clearance of oxidized lipoproteins

BACKGROUND: Recent studies suggest that hypercholesterolemia, an established risk factor for atherosclerosis, is also a risk factor for Alzheimer's disease. The myeloid scavenger receptor CD36 binds oxidized lipoproteins that accumulate with hypercholesterolemia and mediates their clearance from the circulation and peripheral tissues. Recently, we demonstrated that CD36 also binds fibrillar β-amyloid and initiates a signaling cascade that regulates microglial recruitment and activation. As increased lipoprotein oxidation and accumulation of lipid peroxidation products have been reported in Alzheimer's disease, we investigated whether β-amyloid altered oxidized lipoprotein clearance via CD36. METHODS: The availability of mice genetically deficient in class A (SRAI & II) and class B (CD36) scavenger receptors has facilitated studies to discriminate their individual actions. Using primary microglia and macrophages, we assessed the impact of Aβ on: (a) cholesterol ester accumulation by GC-MS and neutral lipid staining, (b) binding, uptake and degradation of (125)I-labeled oxidized lipoproteins via CD36, SR-A and CD36/SR-A-independent pathways, (c) expression of SR-A and CD36. In addition, using mice with targeted deletions in essential kinases in the CD36-signaling cascade, we investigated whether Aβ-CD36 signaling altered metabolism of oxidized lipoproteins. RESULTS: In primary microglia and macrophages, Aβ inhibited binding, uptake and degradation of oxidized low density lipoprotein (oxLDL) in a dose-dependent manner. While untreated cells accumulated abundant cholesterol ester in the presence of oxLDL, cells treated with Aβ were devoid of cholesterol ester. Pretreatment of cells with Aβ did not affect subsequent degradation of oxidized lipoproteins, indicating that lysosomal accumulation of Aβ did not disrupt this degradation pathway. Using mice with targeted deletions of the scavenger receptors, we demonstrated that Aβ inhibited oxidized lipoprotein binding and its subsequent degradation via CD36, but not SRA, and this was independent of Aβ-CD36-signaling. Furthermore, Aβ treatment decreased CD36, but not SRA, mRNA and protein, thereby reducing cell surface expression of this oxLDL receptor. CONCLUSIONS: Together, these data demonstrate that in the presence of β-amyloid, CD36-mediated clearance of oxidized lipoproteins is abrogated, which would promote the extracellular accumulation of these pro-inflammatory lipids and perpetuate lipid peroxidation

Reverse cardio-oncology:Exploring the effects of cardiovascular disease on cancer pathogenesis

The field of cardio-oncology has emerged in response to the increased risk of cardiovascular disease (CVD) in patients with cancer. However, recent studies suggest a more complicated CVD-cancer relationship, wherein development of CVD, either prior to or following a cancer diagnosis, can also lead to increased risk of cancer and worse outcomes for patients. In this review, we describe the current evidence base, across epidemiological as well as preclinical studies, which supports the emerging concept of ‘reverse-cardio oncology’, or CVD-induced acceleration of cancer pathogenesis

Parents’ Pandemic NICU Experience in the United States: A Qualitative Study

Background Prior to the COVID-19 pandemic, parents of infants in the Neonatal Intensive Care Unit (NICU) frequently reported high levels of stress, uncertainty, and decreased parenting confidence. Early research has demonstrated that parents have had less access to their infants in the hospital due to restrictions on parental presence secondary to the pandemic. It is unknown how parents have perceived their experiences in the NICU since the beginning of the COVID-19 pandemic. The purpose of this study was to describe the lived experience of parents who had an infant in the NICU in the context of the COVID-19 pandemic to inform healthcare providers and policy makers for future development of policies and care planning. Methods The study design was a qualitative description of the impact of the COVID-19 pandemic on parents’ experiences of having an infant in the NICU. Free-text responses to open-ended questions were collected as part of a multi-method study of parents’ experiences of the NICU during the first six months of the pandemic. Participants from the United States were recruited using social media platforms between the months of May and July of 2020. Data were analyzed using a reflexive thematic approach. Findings Free-text responses came from 169 parents from 38 different states in the United States. Three broad themes emerged from the analysis: (1) parents’ NICU experiences during the COVID-19 pandemic were emotionally isolating and overwhelming, (2) policy changes restricting parental presence created disruptions to the family unit and limited family-centered care, and (3) interactions with NICU providers intensified or alleviated emotional distress felt by parents. A unifying theme of experiences of emotional distress attributed to COVID-19 circumstances ran through all three themes. Conclusions Parents of infants in the NICU during the first six months of the COVID-19 pandemic experienced emotional struggles, feelings of isolation, lack of family-centered care, and deep disappointment with system-level decisions. Moving forward, parents need to be considered essential partners in the development of policies concerning care of and access to their infants. Background The COVID-19 pandemic created unprecedented conditions for administrators and clinicians working in Neonatal Intensive Care Units (NICU) and greatly affected parents of infants requiring hospitalization. Prior to the COVID-19 pandemic, parents of infants admitted to a NICU reported high levels of stress, anxiety, uncertainty, and decreased parenting confidence when compared to parents of healthy full-term infants [1,2,3,4,5,6]. Approximately 28–40% of mothers of infants admitted to a NICU were diagnosed with a new mental illness, such as depression or perinatal post-traumatic stress disorder [7]. Fathers of infants requiring NICU hospitalization also reported significant stress and need for reassurance and support [8, 9]

Linking the Green and Brown Worlds: the Prevalence and Effect of Multichannel Feeding in Food Webs

Recent advances in food‐web ecology highlight that most real food webs (1) represent an interplay between producer‐ and detritus‐based webs and (2) are governed by consumers which are rampant omnivores; feeding on varied prey across trophic levels and resource channels. A possible avenue to unify these advances comes from models demonstrating that predators feeding on distinctly different channels may stabilize food webs. Empirical studies suggest many consumers engage in such behavior by feeding on prey items from both living‐autotroph (green) and detritus‐based (brown) webs, what we term “multichannel feeding,” yet we know little about how common such feeding is across systems and trophic levels, or its effect on system stability. Considering 23 empirical webs, we find that multichannel feeding is equally common across terrestrial, freshwater, and marine systems, with \u3e50% of consumers classified as multichannel consumers. Multichannel feeding occurred most often at the first consumer level, indicating that most taxa at the herbivore/detritivore level are more aptly described as multichannel consumers, and that such feeding is not restricted to predators. We next developed a simple four‐compartment nutrient cycling model for consumers eating both autotrophs and detritus with separate parameter sets to represent aquatic vs. terrestrial ecosystems. Modeling results showed that, across terrestrial and aquatic ecosystems, multichannel feeding is stabilizing at low attack rates on autotrophs or when attack rates are asymmetric (moderate on autotrophs while low on detritus), but destabilizing at high attack rates on autotrophs, compared to herbivory‐ or detritivory‐only models. The set of conditions with stable webs with multichannel consumers is narrower, however, for aquatic systems, suggesting that multichannel feeding may generally be more stabilizing in terrestrial systems. Together, our results demonstrate that multichannel feeding is common across ecosystems and may be a stabilizing force in real webs that have consumers with low or asymmetric attack rates

Experimental Inoculation of House Sparrows (\u3ci\u3ePasser domesticus\u3c/i\u3e) with Buggy Creek Virus

We performed experimental inoculations of house sparrows (Passer domesticus) with Buggy Creek virus (BCRV), a poorly known alphavirus (Togaviridae) vectored primarily by the swallow bug (Hemiptera: Cimicidae: Oeciacus vicarius) that is an ectoparasite of the cliff swallow (Petrochelidon pyrrhonota) and house sparrow. Viremias were detected by plaque assay in two of six birds on days 1–3 postinoculation; viremia was highest on day 2. Viral RNA was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in blood of six of 12 birds ranging from day 1 to day 15 postinoculation. Infectious BCRV was detected in nasopharyngeal swab samples from two birds by plaque assay. Three control birds that were housed with viremic individuals showed evidence of BCRV RNA in blood (by RT-PCR), suggesting possible bird-to-bird transmission of this virus. Viral RNA also was detected by RT-PCR in brain and skin tissue of six birds on necropsy at the end of the 16-day experiment. Introduced house sparrows are apparently a competent amplifying host for BCRV, and their presence year-round at cliff swallow colonies may facilitate persistence of the virus locally, especially when cliff swallows abandon a site temporarily. The findings that BCRV can be shed orally, that it persists in bird skin, and that control birds could apparently be infected by conspecifics suggest that this virus may be transmitted from bird to bird in the crowded conditions of many cliff swallow colonies

Experimental Inoculation of House Sparrows (\u3ci\u3ePasser domesticus\u3c/i\u3e) with Buggy Creek Virus

We performed experimental inoculations of house sparrows (Passer domesticus) with Buggy Creek virus (BCRV), a poorly known alphavirus (Togaviridae) vectored primarily by the swallow bug (Hemiptera: Cimicidae: Oeciacus vicarius) that is an ectoparasite of the cliff swallow (Petrochelidon pyrrhonota) and house sparrow. Viremias were detected by plaque assay in two of six birds on days 1–3 postinoculation; viremia was highest on day 2. Viral RNA was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in blood of six of 12 birds ranging from day 1 to day 15 postinoculation. Infectious BCRV was detected in nasopharyngeal swab samples from two birds by plaque assay. Three control birds that were housed with viremic individuals showed evidence of BCRV RNA in blood (by RT-PCR), suggesting possible bird-to-bird transmission of this virus. Viral RNA also was detected by RT-PCR in brain and skin tissue of six birds on necropsy at the end of the 16-day experiment. Introduced house sparrows are apparently a competent amplifying host for BCRV, and their presence year-round at cliff swallow colonies may facilitate persistence of the virus locally, especially when cliff swallows abandon a site temporarily. The findings that BCRV can be shed orally, that it persists in bird skin, and that control birds could apparently be infected by conspecifics suggest that this virus may be transmitted from bird to bird in the crowded conditions of many cliff swallow colonies

Robustness of sex-differences in functional connectivity over time in middle-aged marmosets

Nonhuman primates (NHPs) are an essential research model for gaining a comprehensive understanding of the neural mechanisms of neurocognitive aging in our own species. In the present study, we used resting state functional connectivity (rsFC) to investigate the relationship between prefrontal cortical and striatal neural interactions, and cognitive flexibility, in unanaesthetized common marmosets (Callithrix jacchus) at two time points during late middle age (8 months apart, similar to a span of 5-6 years in humans). Based on our previous findings, we also determine the reproducibility of connectivity measures over the course of 8 months, particularly previously observed sex differences in rsFC. Male marmosets exhibited remarkably similar patterns of stronger functional connectivity relative to females and greater cognitive flexibility between the two imaging time points. Network analysis revealed that the consistent sex differences in connectivity and related cognitive associations were characterized by greater node strength and/or degree values in several prefrontal, premotor and temporal regions, as well as stronger intra PFC connectivity, in males compared to females. The current study supports the existence of robust sex differences in prefrontal and striatal resting state networks that may contribute to differences in cognitive function and offers insight on the neural systems that may be compromised in cognitive aging and age-related conditions such as mild cognitive impairment and Alzheimer\u27s disease