1983 research outputs found
Sort by
Gene family evolution underlies cell-type diversification in the hypothalamus of teleosts
No full textABSTRACTHundreds of cell types form the vertebrate brain, but it is largely unknown how similar these cellular repertoires are between or within species, or how cell type diversity evolves. To examine cell type diversity across and within species, we performed single-cell RNA sequencing of ∼130,000 hypothalamic cells from zebrafish (Danio rerio) and surface- and cave-morphs of Mexican tetra (Astyanax mexicanus). We found that over 75% of cell types were shared between zebrafish and Mexican tetra, which last shared a common ancestor over 150 million years ago. Orthologous cell types displayed differential paralogue expression that was generated by sub-functionalization after genome duplication. Expression of terminal effector genes, such as neuropeptides, was more conserved than the expression of their associated transcriptional regulators. Species-specific cell types were enriched for the expression of species-specific genes, and characterized by the neo-functionalization of members of recently expanded or contracted gene families. Within species comparisons revealed differences in immune repertoires and transcriptional changes in neuropeptidergic cell types associated with genomic differences between surface- and cave-morphs. The single-cell atlases presented here are a powerful resource to explore hypothalamic cell types, and reveal how gene family evolution and the neo- and sub-functionalization of paralogs contribute to cellular diversity.Accepted Manuscrip
Cancel culture: Heterodox self-censorship or the curious case of the dog-which-didn’t-bark
No full textThere is widespread concern that academic freedom is threatened by growing demands for intellectual conformity and attempted censorship from intolerant zealots involving ‘woke wars’ and a ‘cancel culture’ pitting the socially liberal progressive left against the socially conservative right. This study seeks to understand the nature and scope of contemporary threats to academic freedom of expression around the world, especially the role of self-censorship in this process. Part I unpacks the notion of a ‘cancel culture’ in academia, understood as a chilly climate silencing speech deemed derogatory, hostile, factually incorrect, or morally offensive. The research explores processes of self-censorship where scholars are unwilling to express their authentic views in public. Mechanisms potentially driving these processes include heterodox status (cultural minorities out of step with majority views aka fish-out-of-water); institutions (constitutional principles, legal frameworks and administrative regulations used by educational authorities to govern academic speech); culture (attitudes, values, and social norms towards free speech); and academic status (inequalities in academic power, security, gender, and age). To establish empirical evidence, Part II sets out the research design. It draws upon new survey data collected from the second ECPR-IPSA World of Political Science survey (WPS-2023), monitoring the background and attitudes of almost 2000 political scientists living and working in around 100 countries worldwide. Part III analyzes the key results, confirming the reluctance of heterodox scholars to challenge majority views in controversial debates. The conclusion in Part IV summarizes the findings, considers their broader implications, and discusses the next steps in the research agenda.Version of Recor
The Relationship between Depression, Stress-Related Neurobiology, and Incident Heart Failure: Understanding the Neurobiological Mechanisms Underlying Exercise as a Preventive Measure
No full textBackground: Numerous evidence underscores the link between high metabolic activity in the brain related to stress (stress-related neural network activity, SNA) and increased risk of cardiovascular disease (CVD) events, including heart failure (HF). Our recent study has demonstrated that physical activity (PA) can effectively decrease SNA levels in a dose-dependent manner. Based on this compelling evidence, we hypothesize that PA may decrease the risk of incident HF in part through a reduction in SNA.
Method: Self-reported PA data were acquired from Mass General Brigham (MGB) Biobank participants. The metabolic equivalent of task minutes per week (MET*minutes/week) was calculated and categorized according to current PA recommendations ( 500 and ≥ 500 METmin/wk). In a subset with 18F-fluorodeoxyglucose positron emission tomography imaging (n=679), SNA was measured as a ratio of amygdalar to ventromedial prefrontal cortical activity (vmPFC). Subsequent HF and baseline CVD risk factor data were obtained using ICD Codes. Linear and Cox regression models were employed to evaluate the relationship between PA vs. HF risk. Mediation analysis was used to test whether PA’s impact on SNA significantly mediated the association between PA and HF.
Results: Among 48,673 participants (median age 60 years [IQR 44 - 70], 39.5% male). PA within recommended level associated with a lower risk of subsequent HF (hazard ratio (HR) [95% confidence interval (CI)]: 0.829 [ 0.743, 0.926], p 0.001). Mediation analysis showed that PA reduces HF risk in part via reductions in SNA, accounting for 9.1% of the total relationship between PA and HF risk (p 0.05). Moreover, among individuals with pre-existing depression and/or anxiety, PA was associated with greater reductions in ten-year HF risk compared to those 28 without depression and/or anxiety (HR [95% CI]: 0.836 [0.785, 0.891] vs. 0.882 [0.858, 0.907], p- interaction=0.048).
Conclusion: PA associates with reductions in SNA activity and subsequent HF risk. Notably, this reduction is greater among those with pre-existing depression and/or anxiety. Moreover, the mechanism by which PA reduces HF risk may involve salutary effects on stress-related neural pathways
Tutorial: Avoiding and Correcting Sample-Induced Spherical Aberration Artifacts in 3D Fluorescence Microscopy
No full textSpherical Aberration (SA) occurs when light rays entering at different points of a spherical lens are not focused to the same point of the optical axis. SA that occurs inside the lens elements of a fluorescence microscope is well understood and corrected for. However, SA is also induced when light passes through an interface of refractive index (RI) mismatched substances (i.e. a discrepancy between the RI of the immersion medium and the RI of the sample). SA due to RI mismatches has many deleterious effects on imaging. Perhaps most important for 3D imaging is that the distance the image plane moves in a sample is not equivalent to the distance travelled by an objective (or stage) during Z-stack acquisition. This non-uniform translation along the Z-axis gives rise to artifactually elongated images (if the objective is immersed in a higher RI medium than the sample) or compressed images (if the objective is immersed in a lower RI medium than the sample) and alters the optimal axial sampling rate. In this Tutorial, we describe why this distortion occurs, how it impacts quantitative measurements and axial resolution and what can be done to avoid SA and thereby prevent distorted images. In addition, this tutorial aims to better inform researchers of how to correct RI mismatch-induced axial distortions and provides a practical ImageJ/Fiji-based tool to reduce the prevalence of volumetric measurement errors and lost axial resolution.Accepted Manuscrip
Effectiveness of CoronaVac Among Children 3 to 5 During the Omicron SARS-CoV-2 Outbreak
No full textAbstract
The outbreak of the B.1.1.529 lineage of SARS-CoV-2 (omicron) has caused an unprecedented number of Covid-19 cases, including pediatric hospital admissions. Policymakers urgently need evidence of vaccine effectiveness in children to balance the costs and benefits of vaccination campaigns, but the evidence is sparse or non-existing. Leveraging a population-based cohort of 490,694 children aged 3–5 years, we estimated the effectiveness of administering a two-dose schedule, 28 days apart, of CoronaVac using inverse probability-weighted survival regression models to estimate hazard ratios of complete immunization over non-vaccination, accounting for time-varying vaccination exposure and relevant confounders. The study was conducted between December 6, 2021, and February 26, 2022, during the omicron outbreak in Chile. The estimated vaccine effectiveness was 38.2% (95%CI, 36.5–39.9) against Covid-19, 64.6% (95%CI, 49.6–75.2) against hospitalization, and 69.0% (95%CI, 18.6–88.2) to prevent intensive care unit admission. The effectiveness was modest; however, protection against severe disease remained high.Accepted Manuscrip
Precision Cosmology with Emission-Line Galaxies
No full textIn the recent decade, low redshift weak lensing surveys have shown a ~2-3σ tension compared to cosmic microwave background (CMB) anisotropy surveys when it comes to measuring the amplitude of matter clustering, σ8. If the same tension is found at a higher precision, then it could potentially point to the existence beyond ΛCDM physics. Next-generation surveys such as the Dark Energy Spectroscopic Instrument aims to answer tensions like these by probing the Universe at higher redshift, especially with emission-line galaxies (ELG) that trace large-scale structure in the critical turnover period when the Universe was being affected by dark energy substantially for the first time. This dissertation aims to address such cosmological tensions by (i) improving the DESI ELG target selection to secure a high yield of reliable spectroscopic redshifts, (ii) studying the impact of biases arising from galaxy window function estimation, and (iii) cross-correlating DESI-like ELGs from the Legacy Surveys and Planck CMB lensing. The findings of this work resulted in (i) validating a DESI ELG target selection algorithm that meets survey specifications, (ii) detecting biases in galaxy window function estimation that can shift the amplitude of clustering inference by ~2.6% and degrade the error ellipse of the galaxy linear bias-A_s plane by ~25%, and (iii) providing a high-precision measurement of σ8 = 0.696 ± 0.028. These findings collectively result in one of the highest tensions in σ8 compared to CMB anisotropy probes. More importantly, these findings show that future cross-correlation analyses of ELGs and CMB lensing will have the power to definitively discern whether the tensions point to new physics
Birth Matters: Examining Contextual Risk and Protective Factors for Maternal Postpartum Depression
No full textThe transition into motherhood can be a challenging time for many women as they traverse the vast physical, social, and emotional changes that occur during pregnancy, birth, and the postpartum period. Postpartum depression (PPD) is one of the most common complications after childbirth. Not only is PPD a debilitating condition that severely disrupts a mother’s day to day functioning, but it can negatively impact child development and family health and has many broad implications for public health. While the etiology of PPD is still unclear in the research literature, it is likely a constellation of biological, environmental, and cultural risk factors coupled with psychosocial life stressors that impact the risk of PPD. The focus of my dissertation is the gap in research in understanding how events that occur during birth itself and contextual factors around birth may increase the risk of maternal PPD. This dissertation consists of three epidemiological studies that leverage national and statewide data from the Pregnancy Risk Assessment and Monitoring System (PRAMS). Quantitative analytic methods were employed to assess how multiple contextual factors in the birthing experience may act as risk or protective factors for maternal PPD.
In Chapter 1, we investigated how having a cesarean section (C-section) delivery influenced the risk of post-partum depressive symptoms, using a large and nationally representative sample of women. In this study, we found that women in the study sample who had a first-time C-sections had higher odds of having post-partum depressive symptoms compared to women who had a vaginal delivery. These findings persisted even after adjusting for clinically relevant covariates and the most prominent risk factors for post-partum depression. These results were consistent and similar among first-time mothers and mothers with no prior history of depression.
In Chapter 2, focusing on a different contextual factor during birth, we investigated whether utilizing a midwife or doula, as opposed to standard obstetric care, impacted a mother’s risk of having a surgical cesarean delivery. From our quantitative analysis we found that women in the study sample who had care from a doula or midwife had a modest decrease in risk of a C-section compared to women who did not have doula or midwifery support. This decrease in risk was most noticeable for women who had previously had a C-section, as women who had a doula or midwife were more likely to successfully have a vaginal birth after cesarean (VBAC) compared to women who did not.
In the final study in Chapter 3, we examined the intersectional relationship and collective influence of racial and ethnic identity and maternal nativity on risk of experiencing PPD symptoms. From the quantitative analyses, we found that the prevalence and risk of PPD symptoms varied significantly by race/ethnicity and nativity status, with the highest risk present among those born outside of the US. Most racial/ethnic minority mothers in our sample, both US-born and non-US born, had a higher risk of PPD symptoms compared to US-born non-Hispanic White mothers. From the stratified analyses we found that most immigrant mothers had higher risk of PPD symptoms compared to their US-born racial/ethnic counterparts. These differences in risk remained even after accounting for socioeconomic, medical, and mental health risk factors. The potential explanatory pathways and reasons for the stark disparities in maternal postpartum depression observed in our study by nativity and race/ethnicity are elaborated upon in our discussion.
When these dissertation studies are taken together, the findings illustrate how birth context can matter for maternal mental health. From the first study, it was evident that the method of delivery and birth can be a protective or risk factor for PPD symptoms. The second study expanded these findings to suggest that the type of birth attendant impacts the method of birth. The last study illustrated how where the mother herself was born mattered for postpartum mental health and recovery. This research fills gaps in the current research literature on contextual risk factors and protective predictors of PPD in US women. It adds to a growing body of research in this area that ultimately may lead to improvements in maternal health and wellbeing
Remote Patient Monitoring — Overdue or Overused?
No full textAs the use of remote patient monitoring services grows—driven by health care limitations imposed by the COVID-19 pandemic—clinicians, payers, and patients face important questions regarding the volume, value, and appropriate use of this care model.Author's Origina