A Conserved Noncoding Locus Regulates Random Monoallelic Xist Expression across a Topological Boundary

cis-Regulatory communication is crucial in mammalian development and is thought to be restricted by the spatial partitioning of the genome in topologically associating domains (TADs). Here, we discovered that the Xist locus is regulated by sequences in the neighboring TAD. In particular, the promoter of the noncoding RNA Linx (LinxP) acts as a long-range silencer and influences the choice of X chromosome to be inactivated. This is independent of Linx transcription and independent of any effect on Tsix, the antisense regulator of Xist that shares the same TAD as Linx. Unlike Tsix, LinxP is well conserved across mammals, suggesting an ancestral mechanism for random monoallelic Xist regulation. When introduced in the same TAD as Xist, LinxP switches from a silencer to an enhancer. Our study uncovers an unsuspected regulatory axis for X chromosome inactivation and a class of cis-regulatory effects that may exploit TAD partitioning to modulate developmental decisions.Galupa et al. uncover elements important for Xist regulation in its neighboring TAD and reveal that these elements can influence gene regulation both within and between topological domains. These findings, in a context where dynamic, developmental expression is necessary, challenge current models for TAD-based gene-regulatory landscapes

Lives versus Livelihoods? Perceived economic risk has a stronger association with support for COVID-19 preventive measures than perceived health risk

This paper examines whether compliance with COVID-19 mitigation measures is motivated by wanting to save lives or save the economy (or both), and which implications this carries to fight the pandemic. National representative samples were collected from 24 countries (N = 25,435). The main predictors were (1) perceived risk to contract coronavirus, (2) perceived risk to suffer economic losses due to coronavirus, and (3) their interaction effect. Individual and country-level variables were added as covariates in multilevel regression models. We examined compliance with various preventive health behaviors and support for strict containment policies. Results show that perceived economic risk consistently predicted mitigation behavior and policy support—and its effects were positive. Perceived health risk had mixed effects. Only two significant interactions between health and economic risk were identified—both positive

Regulation of single-cell genome organization into TADs and chromatin nanodomains.

Super-resolution microscopy identifies sub-topologically associating domain (TAD) nanodomains and intercellular heterogeneity in TAD conformation and insulation. Cohesin or CTCF depletion regulates distinct types of chromatin contacts at the TAD but not nanodomain level.The genome folds into a hierarchy of three-dimensional structures within the nucleus. At the sub-megabase scale, chromosomes form topologically associating domains (TADs)(1-4). However, how TADs fold in single cells is elusive. Here, we reveal TAD features inaccessible to cell population analysis by using super-resolution microscopy. TAD structures and physical insulation associated with their borders are variable between individual cells, yet chromatin intermingling is enriched within TADs compared to adjacent TADs in most cells. The spatial segregation of TADs is further exacerbated during cell differentiation. Favored interactions within TADs are regulated by cohesin and CTCF through distinct mechanisms: cohesin generates chromatin contacts and intermingling while CTCF prevents inter-TAD contacts. Furthermore, TADs are subdivided into discrete nanodomains, which persist in cells depleted of CTCF or cohesin, whereas disruption of nucleosome contacts alters their structural organization. Altogether, these results provide a physical basis for the folding of individual chromosomes at the nanoscale

Boron and calcium sprayed on 'Fuyu' persimmon tree prevent skin cracks, groove and browning of fruit during cold storage Boro e cálcio pulverizado em árvores de caqui "Fuyu" previnem fissuras, estrias e escurecimento do fruto durante o armazenamento refrigerado

Flesh softening, skin browning and rotting are chief problems during cold storage (CS) of 'Fuyu' Persimmon. We studied the effects of boron (B) and calcium (Ca) sprayed on the trees during three consecutive years, on the development of skin cracks, grooves and browning in persimmon fruit under CS in Farroupilha, RS, Brazil (29&deg;31' south, 51&deg;21' west, about 750 m altitude). A homogeneous orchard area of 0.5 ha was delimitated and three sets of five plants for each treatment were randomly selected. The persimmon trees were sprayed at a 20 day interval, from 15th January until harvest, for three consecutive years, with: T1) water; T2) calcium nitrate at 0.5% (m/v); T3) calcium chloride at 0.5% (m/v); and T4) boron at 0.3% (m/v). The fruit were harvest with orange-reddish colour; 18-20&deg;Brix, pulp firmness of 45 to 60N, and kept under CS at 0&plusmn;1&deg;C for 45 days. The fruits were evaluated immediately before CS, after six hours at 23&plusmn;2&deg;C after removal from CS, and after four days at 23&plusmn;2&deg;C after removal from CS. Equally boron and calcium sprayed on the trees prevented skin cracks, skin grooves and skin browning. Besides, when boron was sprayed on the trees, the mentioned effects were additive in the following year.<br>As principais alterações indesejáveis observadas no período pós-colheita de caquis em armazenamento refrigerado (AR) são a perda de firmeza de polpa, e a ocorrência de escurecimento epidérmico e de podridões. Este trabalho teve por objetivo principal estudar as respostas da aplicação de boro (B) e cálcio (Ca), em três safras sucessivas, na prevenção da ocorrência de fissuras, estrias e escurecimento epidérmico de caquis "Fuyu". No pomar (Farroupilha-RS-Brasil, 29&deg;31' Sul, 51&deg;21' Oeste, aproximadamente 750m altitude) delimitou-se uma área homogênea de 0,5ha., marcando-se, ao acaso, três repetições de cinco plantas para cada tratamento: T1 - controle, caquizeiros não-pulverizados com B e Ca; T2 - pulverizações com Nitrato de Ca 0,5% (m/v); T3 - pulverizações com Cloreto de Ca 0,5% (m/v); e T4 - pulverizações com B 0,3% (m/v). As aplicações foram realizadas em três anos sucessivos a partir de 15 de janeiro a intervalos de 20 dias. Foram colhidos os caquis na coloração alaranjado-avermelhada, com 18-20&deg;Brix e 45 a 60N, que posteriormente foram armazenados em AR a 0&plusmn;1&deg;C por 45 dias. As avaliações foram realizadas no dia do armazenamento, após seis horas a 23&plusmn;2&deg;C a partir da retirada AR, e após quatro dias a 23&plusmn;2&deg;C a partir da retirada do AR. Foi avaliada a ocorrência de frutas com fissuras, estrias e escurecimento epidérmico. Comprovou-se o efeito benéfico da aplicação de B ou Ca na prevenção de fissuras, estrias e escurecimento epidérmico. Adicionalmente, foi detectado o incremento da resposta à aplicação de B, que, além de prevenir (à semelhança das aplicações com Ca), apresentou efeito aditivo no segundo ano. O resultado sugere que as respostas às aplicações com B são progressivas

Immunocompromised patients with acute respiratory distress syndrome : Secondary analysis of the LUNG SAFE database

The aim of this study was to describe data on epidemiology, ventilatory management, and outcome of acute respiratory distress syndrome (ARDS) in immunocompromised patients. Methods: We performed a post hoc analysis on the cohort of immunocompromised patients enrolled in the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) study. The LUNG SAFE study was an international, prospective study including hypoxemic patients in 459 ICUs from 50 countries across 5 continents. Results: Of 2813 patients with ARDS, 584 (20.8%) were immunocompromised, 38.9% of whom had an unspecified cause. Pneumonia, nonpulmonary sepsis, and noncardiogenic shock were their most common risk factors for ARDS. Hospital mortality was higher in immunocompromised than in immunocompetent patients (52.4% vs 36.2%; p < 0.0001), despite similar severity of ARDS. Decisions regarding limiting life-sustaining measures were significantly more frequent in immunocompromised patients (27.1% vs 18.6%; p < 0.0001). Use of noninvasive ventilation (NIV) as first-line treatment was higher in immunocompromised patients (20.9% vs 15.9%; p = 0.0048), and immunodeficiency remained independently associated with the use of NIV after adjustment for confounders. Forty-eight percent of the patients treated with NIV were intubated, and their mortality was not different from that of the patients invasively ventilated ab initio. Conclusions: Immunosuppression is frequent in patients with ARDS, and infections are the main risk factors for ARDS in these immunocompromised patients. Their management differs from that of immunocompetent patients, particularly the greater use of NIV as first-line ventilation strategy. Compared with immunocompetent subjects, they have higher mortality regardless of ARDS severity as well as a higher frequency of limitation of life-sustaining measures. Nonetheless, nearly half of these patients survive to hospital discharge. Trial registration: ClinicalTrials.gov, NCT02010073. Registered on 12 December 2013