The recent discovery of gravitational waves from mergers of ∼10 M⊙ black hole binaries has stimulated interested in primordial black hole (PBH) dark matter in this mass range. Microlensing and ...dynamical constraints exclude all of the dark matter in compact objects with a delta function mass function in the range 10−7≲M/M⊙≲105. However it has been argued that all of the dark matter could be composed of compact objects in this range with an extended mass function. We explicitly recalculate the microlensing and dynamical constraints for compact objects with an extended mass function which replicates the PBH mass function produced by inflation models. We find that the microlensing and dynamical constraints place conflicting constraints on the width of the mass function, and do not find a mass function which satisfies both constraints.
The detection of gravitational waves from mergers of tens of Solar mass black hole binaries has led to a surge in interest in primordial black holes (PBHs) as a dark matter candidate. We aim to ...provide a (relatively) concise overview of the status of PBHs as a dark matter candidate, circa Summer 2020. First we review the formation of PBHs in the early Universe, focussing mainly on PBHs formed via the collapse of large density perturbations generated by inflation. Then we review the various current and future constraints on the present day abundance of PBHs. We conclude with a discussion of the key open questions in this field.
Gender stereotypes have descriptive components, or beliefs about how males and females typically act, as well as prescriptive components, or beliefs about how males and females should act. For ...example, women are supposed to be nurturing and avoid dominance, and men are supposed to be agentic and avoid weakness. However, it is not clear whether people hold prescriptive gender stereotypes about children of different age groups. In addition, research has not addressed prescriptive gender stereotypes for the elderly. The current research measured prescriptive gender stereotypes for children, adults, and elderly men and women in 3 studies to (a) compare how prescriptive gender stereotypes change across age groups and (b) address whether stereotypes of males are more restrictive than stereotypes of females. Students (Studies 1 and 2) and community members (Study 3), which were all U.S. and majority White samples, rated how desirable it was for different target groups to possess a list of characteristics from 1
) to 9 (
). The target age groups included toddlers, elementary-aged, adolescent, young adult, adult, and elderly males and females. The list of 21 characteristics was created to encompass traits and behaviors relevant across a wide age range. In a meta-analysis across studies, prescriptive stereotypes were defined as characteristics displaying a sex difference of
> 0.40 and an average rating as desirable for positive prescriptive stereotypes (PPS) or undesirable for negative proscriptive stereotypes (NPS) for male or females of each age group. Results replicated previous research on prescriptive stereotypes for adults: Women should be communal and avoid being dominant. Men should be agentic, independent, masculine in appearance, and interested in science and technology, but avoid being weak, emotional, shy, and feminine in appearance. Stereotypes of boys and girls from elementary-aged to young adults still included these components, but stereotypes of toddlers involved mainly physical appearance and play behaviors. Prescriptive stereotypes of elderly men and women were weaker. Overall, boys and men had more restrictive prescriptive stereotypes than girls and women in terms of strength and number. These findings demonstrate the applicability of prescriptive stereotypes to different age groups.
The T cell infiltrates that are formed in human cancers are a modifier of natural disease progression and also determine the probability of clinical response to cancer immunotherapies. Recent ...technological advances that allow the single-cell analysis of phenotypic and transcriptional states have revealed a vast heterogeneity of intratumoural T cell states, both within and between patients, and the observation of this heterogeneity makes it critical to understand the relationship between individual T cell states and therapy response. This Review covers our current knowledge of the T cell states that are present in human tumours and the role that different T cell populations have been hypothesized to play within the tumour microenvironment, with a particular focus on CD8
T cells. The three key models that are discussed herein are as follows: (1) the dysfunction of T cells in human cancer is associated with a change in T cell functionality rather than inactivity; (2) antigen recognition in the tumour microenvironment is an important driver of T cell dysfunctionality and the presence of dysfunctional T cells can hence be used as a proxy for the presence of a tumour-reactive T cell compartment; (3) a less dysfunctional population of tumour-reactive T cells may be required to drive a durable response to T cell immune checkpoint blockade.
Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 originated from Wuhan, China, in December 2019 and rapidly spread to other areas worldwide. Since then, coronavirus disease 2019 (COVID-19) ...has reached pandemic proportions with >570 000 deaths globally by mid-July 2020. The magnitude of the outbreak and the potentially severe clinical course of COVID-19 has led to a burst of scientific research on this novel coronavirus and its host receptor ACE (angiotensin-converting enzyme)-2. ACE2 is a homolog of the ACE that acts on several substrates in the renin-Ang (angiotensin) system. With unprecedented speed, scientific research has solved the structure of SARS-CoV-2 and imaged its binding with the ACE2 receptor. In SARS-CoV-2 infection, the viral S (spike) protein receptor-binding domain binds to ACE2 to enter the host cell. ACE2 expression in the lungs is relatively low, but it is present in type II pneumocytes-a cell type also endowed with TMPRSS2 (transmembrane protease serine 2). This protease is critical for priming the SARS-CoV-2 S protein to complex with ACE2 and enter the cells. Herein, we review the current understanding of the interaction of SARS-CoV-2 with ACE2 as it has rapidly unfolded over the last months. While it should not be assumed that we have a complete picture of SARS-CoV-2 mechanism of infection and its interaction with ACE2, much has been learned with clear therapeutic implications. Potential therapies aimed at intercepting SARS-CoV-2 from reaching the full-length membrane-bound ACE2 receptor using soluble ACE2 protein and other potential approaches are briefly discussed as well.
Sex-specific differences in the epidemiology, pathophysiology, clinical presentation, clinical treatment, and clinical outcomes of atrial fibrillation (AF), sustained ventricular arrhythmias, and ...sudden cardiac death are recognized. Sex hormones cause differences in cardiac electrophysiological parameters between men and women that may affect the risk for arrhythmias. The incidence and prevalence of AF is lower in women than in men. However, because women live longer and AF prevalence increases with age, the absolute number of women with AF exceeds that of men. Women with AF are more symptomatic, present with more atypical symptoms, and report worse quality of life in comparison with men. Female sex is an independent risk factor for death or stroke attributable to AF. Oral anticoagulation therapy for stroke prevention has similar efficacy for men and women, but older women treated with warfarin have a higher residual risk of stroke in comparison with men. Women with AF are less likely to receive rhythm control antiarrhythmic drug therapy, electric cardioversion, or catheter ablation in comparison with men. The incidence and prevalence of sustained ventricular arrhythmias and sudden cardiac death are lower in women than in men. Women receiving implantable cardioverter defibrillators for primary prevention of sudden cardiac death are less likely to experience sustained ventricular arrhythmias in comparison with men. In contrast, women receiving a cardiac resynchronization therapy implantable cardioverter defibrillator for the treatment of heart failure are more likely to benefit than men. Women are less likely to be referred for implantable cardioverter defibrillator therapy despite current guideline recommendations. Women are more likely to experience a significant complication related to implantable cardioverter defibrillator implantation in comparison with men. Whether sex differences in treatment decisions reflect patient preferences or treatment biases requires further study.
In applying social role theory to account for the content of a wide range of stereotypes, this research tests the proposition that observations of groups' roles determine stereotype content (Eagly & ...Wood, 2012). In a novel test of how stereotypes can develop from observations, preliminary research collected participants' beliefs about the occupational roles (e.g., lawyer, teacher, fast food worker, chief executive officer, store clerk, manager) in which members of social groups (e.g., Black women, Hispanics, White men, the rich, senior citizens, high school dropouts) are overrepresented relative to their numbers in the general population. These beliefs about groups' typical occupational roles proved to be generally accurate when evaluated in relation to data from the Bureau of Labor Statistics. Then, correlational studies predicted participants' stereotypes of social groups from the attributes ascribed to group members' typical occupational roles (Studies 1a, 1b, and 1c), the behaviors associated with those roles (Study 2), and the occupational interest profile of the roles (Study 3). As predicted by social role theory, beliefs about the attributes of groups' typical roles were strongly related to group stereotypes on both communion and agency/competence. In addition, an experimental study (Study 4) demonstrated that when social groups were described with changes to their typical social roles in the future, their projected stereotypes were more influenced by these future roles than by their current group stereotypes, thus supporting social role theory's predictions about stereotype change. Discussion considers the implications of these findings for stereotype change and the relation of social role theory to other theories of stereotype content.
Meiotic double-strand breaks (DSBs) are generated and repaired in a highly regulated manner to ensure formation of crossovers (COs) while also enabling efficient non-CO repair to restore genome ...integrity. We use structured-illumination microscopy to investigate the dynamic architecture of DSB repair complexes at meiotic recombination sites in relationship to the synaptonemal complex (SC). DSBs resected at both ends are converted into inter-homolog repair intermediates harboring two populations of BLM helicase and RPA, flanking a single population of MutSγ. These intermediates accumulate until late pachytene, when repair proteins disappear from non-CO sites and CO-designated sites become enveloped by SC-central region proteins, acquire a second MutSγ population, and lose RPA. These and other data suggest that the SC may protect CO intermediates from being dismantled inappropriately and promote CO maturation by generating a transient CO-specific repair compartment, thereby enabling differential timing and outcome of repair at CO and non-CO sites.
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•Recombination proteins adopt distinct spatial architecture at meiotic crossover sites•Recombination site architecture undergoes dynamic changes during meiotic progression•The synaptonemal complex envelops crossover-designated recombination intermediates•Crossover and non-crossover repair are completed in spatially distinct compartments
Structured-illumination microscopy of meiotic chromosomes reveals that distinct architecture and spatial compartmentalization are associated with differential timing and outcome of repair at crossover and non-crossover sites.
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