Hierarchical folding and reorganization of chromosomes are linked to transcriptional changes in cellular differentiation.

Mammalian chromosomes fold into arrays of megabase-sized topologically associating domains (TADs), which are arranged into compartments spanning multiple megabases of genomic DNA. TADs have internal substructures that are often cell type specific, but their higher-order organization remains elusive. Here, we investigate TAD higher-order interactions with Hi-C through neuronal differentiation and show that they form a hierarchy of domains-within-domains (metaTADs) extending across genomic scales up to the range of entire chromosomes. We find that TAD interactions are well captured by tree-like, hierarchical structures irrespective of cell type. metaTAD tree structures correlate with genetic, epigenomic and expression features, and structural tree rearrangements during differentiation are linked to transcriptional state changes. Using polymer modelling, we demonstrate that hierarchical folding promotes efficient chromatin packaging without the loss of contact specificity, highlighting a role far beyond the simple need for packing efficiency.

Efficacy of Various Application Methods of Fluensulfone for Managing Root-knot Nematodes in Vegetables.

Fluensulfone is a new nematicide in the flouroalkenyl chemical group. A field experiment was conducted in 2012 and 2013 to evaluate the efficacy of various application methods of fluensulfone for control of Meloidogyne spp. in cucumber (Cucumis sativus). Treatments of fluensulfone (3.0 kg a.i./ha) were applied either as preplant incorporation (PPI) or via different drip irrigation methods: drip without pulse irrigation (Drip NP), pulse irrigation 1 hr after treatment (Drip +1P), and treatment at the same time as pulse irrigation (Drip =P). The experiment had eight replications per treatment and also included a PPI treatment of oxamyl (22.5 kg a.i./ha) and a nontreated control. Compared to the control, neither the oxamyl nor the fluensulfone PPI treatments reduced root galling by Meloidogyne spp. in cucumber. Among the drip treatments, Drip NP and Drip +1P reduced root galling compared to the control. Cucumber yield was greater in all fluensulfone treatments than in the control. In a growth-chamber experiment, the systemic activity and phytotoxicity of fluensulfone were also evaluated on tomato (Solanum lycopersicum), eggplant (Solanum melongena), cucumber, and squash (Curcurbita pepo). At the seedling stage, foliage of each crop was sprayed with fluensulfone at 3, 6, and 12 g a.i./liter, oxamyl at 4.8 g a.i./liter, or water (nontreated control). Each plant was inoculated with Meloidogyne incognita juveniles 2 d after treatment. There were six replications per treatment and the experiment was conducted twice. Foliar applications of fluensulfone reduced plant vigor and dry weight of eggplant and tomato, but not cucumber or squash; application of oxamyl had no effect on the vigor or weight of any of the crops. Typically, only the highest rate of fluensulfone was phytotoxic to eggplant and tomato. Tomato was the only crop tested in which there was a reduction in the number of nematodes or galls when fluensulfone or oxamyl was applied to the foliage compared to the nontreated control. This study demonstrates that control of Meloidogyne spp. may be obtained by drip and foliar applications of fluensulfone; however, the systemic activity of fluensulfone is crop specific and there is a risk of phytotoxicity with foliar applications.

Efficacy of Fluensulfone in a Tomato-Cucumber Double Cropping System.

Vegetable crops in the southeastern United States are commonly grown on plastic mulch with two crop cycles produced on a single mulch application. Field trials were conducted in 2013 and 2014 in two locations to evaluate the efficacy of fluensulfone for controlling Meloidogyne spp. when applied through drip irrigation to cucumber in a tomato-cucumber double-cropping system. In the spring tomato crop, 1,3-dichloropropene (1,3-D), fluensulfone, and a resistant cultivar significantly decreased root galling by 91%, 73%, and 97%, respectively, compared to the untreated control. Tomato plots from the spring were divided into split plots for the fall where the main plots were the spring treatment and the subplots were cucumber either treated with fluensulfone (3.0 kg a.i./ha. via drip irrigation) or left untreated. The fall application of fluensulfone improved cucumber vigor and reduced gall ratings compared to untreated subplots. Fluensulfone reduced damage from root-knot nematodes when applied to the first crop as well as provided additional protection to the second crop when it was applied through a drip system.

Increased angiogenic sprouting in poor prognosis FL is associated with elevated numbers of CD163+ macrophages within the immediate sprouting microenvironment.

Follicular lymphoma has considerable clinical heterogeneity, and there is a need for easily quantifiable prognostic biomarkers. Microvessel density has been shown to be a useful prognostic factor based on numerical assessment of vessel numbers within histologic sections in some studies, but assessment of tumor neovascularization through angiogenic sprouting may be more relevant. We therefore examined the smallest vessels, single-staining structures measuring less than 30 microm(2) in area, seen within histologic sections, and confirmed that they were neovascular angiogenic sprouts using extended focal imaging. Tissue microarrays composing diagnostic biopsies from patients at the extremes of survival of follicular lymphoma were analyzed with respect to numbers of these sprouts. This analysis revealed higher angiogenic activity in the poor prognostic group and demonstrated an association between increased sprouting and elevated numbers of infiltrating CD163(+) macrophages within the immediate microenvironment surrounding the neovascular sprout.

Prohormone-substrate peptide sequence recognition by peptidylglycine α-amidating monooxygenase and its reflection in increased glycolate inhibitor potency.

The interactions of nineteen peptide substrates and fifteen analogous peptidomimetic glycolate inhibitors with human peptidylglycine α-amidating monooxygenase (PAM) have been investigated. The substrates and inhibitors are the prohormones of calcitonin and oxytocin and their analogues. PAM both secreted into the medium by and extracted from DMS53 small lung carcinoma cells has been studied. The results show that recognition of the prooxytocin and procalcitonin peptide sequences by the enzyme extends more than four and five amino acid residues, respectively, from their C-termini. This substrate sequence recognition is mirrored by increased inhibitor potency with increased peptide length in the glycolate peptidomimetics. Substitution of the C-terminal penultimate glycine and proline residues of prooxytocin and procalcitonin and their analogues with phenylalanine increases the enzyme binding affinity. However, this changes the binding mode from one that depends on peptide sequence recognition to another primarily determined by the phenylalanine moiety, for both the substrates and analogous glycolate inhibitors.

A National Communication Effort Addressing Maternal Mortality in the United States: Implementation of the Hear Her Campaign.

More than 700 women die each year in the United States from complications related to pregnancy, and considerable racial and ethnic disparities continue to exist. Recognizing the urgent maternal warning signs of pregnancy-related complications, getting an accurate and timely diagnosis and quality care can save lives. In August 2020, the Centers for Disease Control and Prevention, Division of Reproductive Health launched a national communication campaign called "Hear Her" to raise awareness of urgent maternal warning signs during pregnancy and in the year after pregnancy and improve communication between pregnant or postpartum people and their support systems and health care providers. Storytelling is a central strategy to the campaign, which features video stories of women's experiences with pregnancy-related conditions to bring voices to the statistics and to help motivate action. These stories and additional campaign resources are disseminated through a website, digital media, organic (free) and paid social media, earned media, public service announcement distribution, and partners, with increased outreach to disproportionately affected communities. Partners in maternal and child health played an important role from campaign development to outreach and message dissemination. In the first year of the campaign, there were >390,000 unique visitors to the Hear Her website and 180 million impressions (number of times that content was displayed to a user) from digital and social media. Digital media allowed the campaign to reach priority audiences at a time when news and social media had a number of other urgent public health messages related to the COVID-19 pandemic.

Use of mechanical insufflation exsufflation and manual techniques in an intubated adult with COVID-19 positioned in prone-A case study.

BACKGROUND AND PURPOSE: The therapeutic benefits of prone positioning have been described over the last 50 years culminating in a systematic review supporting this management strategy for patients with severe hypoxaemic respiratory failure. Early work detailing treatment approaches for COVID-19 have advocated the use of prone positioning. Limited data exists regarding physiotherapy intervention in patients with COVID-19 owing to the recent emergence of this novel disease. Despite the acknowledged beneficial effects of physiotherapy on secretion clearance and lung recruitment in the general critical care population, there is a lack of evidence pertaining to physiotherapeutic intervention for acutely unwell intubated adults in prone lying. METHODS: This case study report follows the CARE case report guidelines. One patient with COVID-19 pneumonitis who underwent physiotherapy intervention in prone lying is discussed. Informed consent was gained from next of kin for data to be published. RESULTS: Treatment techniques including mechanical insufflation-exsufflation in prone were feasible and well tolerated by this patient with only transient adverse effects noted. Treatment techniques assisted with secretion clearance. DISCUSSION: Further work on safety, feasibility, and efficacy of physiotherapy intervention in patients with and without COVID-19 in prone will contribute to the evidence base on this subject.

Heterokaryon-based reprogramming of human B lymphocytes for pluripotency requires Oct4 but not Sox2.

Differentiated cells can be reprogrammed through the formation of heterokaryons and hybrid cells when fused with embryonic stem (ES) cells. Here, we provide evidence that conversion of human B-lymphocytes towards a multipotent state is initiated much more rapidly than previously thought, occurring in transient heterokaryons before nuclear fusion and cell division. Interestingly, reprogramming of human lymphocytes by mouse ES cells elicits the expression of a human ES-specific gene profile, in which markers of human ES cells are expressed (hSSEA4, hFGF receptors and ligands), but markers that are specific to mouse ES cells are not (e.g., Bmp4 and LIF receptor). Using genetically engineered mouse ES cells, we demonstrate that successful reprogramming of human lymphocytes is independent of Sox2, a factor thought to be required for induced pluripotent stem (iPS) cells. In contrast, there is a distinct requirement for Oct4 in the establishment but not the maintenance of the reprogrammed state. Experimental heterokaryons, therefore, offer a powerful approach to trace the contribution of individual factors to the reprogramming of human somatic cells towards a multipotent state.

SAGE analysis demonstrates increased expression of TOSO contributing to Fas-mediated resistance in CLL.

To identify novel genes involved in the molecular pathogenesis of chronic lymphocytic leukemia (CLL) we performed a serial analysis of gene expression (SAGE) in CLL cells, and compared this with healthy B cells (nCD19(+)). We found a high level of similarity among CLL subtypes, but a comparison of CLL versus nCD19(+) libraries revealed 55 genes that were over-represented and 49 genes that were down-regulated in CLL. A gene ontology analysis revealed that TOSO, which plays a functional role upstream of Fas extrinsic apoptosis pathway, was over-expressed in CLL cells. This finding was confirmed by real-time reverse transcription-polymerase chain reaction in 78 CLL and 12 nCD19(+) cases (P < .001). We validated expression using flow cytometry and tissue microarray and demonstrated a 5.6-fold increase of TOSO protein in circulating CLL cells (P = .013) and lymph nodes (P = .006). Our SAGE results have demonstrated that TOSO is a novel over-expressed antiapoptotic gene in CLL.

Nuclear architecture in stem cells.

Fundamental features of genome regulation depend on the linear DNA sequence, cell type specific modification of DNA and chromatin-associated proteins, which locally control the expression of single genes. Architectural features of genome organization within the three-dimensional (3D) nuclear space establish preferential positioning of genes relative to nuclear subcompartments associated with specific biochemical activities, thereby influencing states of expression. The structural and temporal organization of the genome within the nucleus of stem cells, together with specific features of epigenetic and transcriptional regulation are emerging as key players that influence pluripotency and differentiation.1,2.

Using the Resident Assessment Instrument-Mental Health (RAI-MH) to determine levels of care for individuals with serious mental illness.

This paper outlines the development of an algorithm to determine appropriate levels of care (LOC) for individuals with a serious mental illness (SMI). The algorithm, drew on several domains of the Resident Assessment Instrument-Mental Health (RAI-MH) to support a statistical model that would explain a maximum of variance with the gold standard, a consensus-based global rating of required LOC. The RAI-MH model explained 67.5% of the variance. The validity of the model was further examined by determining how the discrepancy between the current and predicted levels of care related to psychiatric outcomes. The results demonstrated that undersupported clients experienced significant negative psychiatric outcomes compared to clients receiving adequate care. Although the model based on the RAI-MH is not perfect, the results warrant further research to determine its usefulness in predicting required LOC.

Fluensulfone sorption and mobility as affected by soil type.

BACKGROUND: Fluensulfone is a fluoroalkenyl chemical with activity against multiple genera of plant-parasitic nematodes. The adsorption, desorption, and mobility of fluensulfone were evaluated on multiple soils from the USA in laboratory and column experiments. RESULTS: Adsorption data regressed to the logarithmic Freundlich equation resulted in isotherm values of 1.24 to 3.28. Soil adsorption of fluensulfone correlated positively with organic matter (0.67) and clay (0.34), but negatively with sand (-0.54). Fluensulfone soil desorption correlated to pH (0.38) and cation exchange capacity (0.44). Fluensulfone desorption from Arredondo sand soil was 26%, and from other soils ranged from 43 to 70%. In mobility experiments, fluensulfone in the leachate peaked at 3 h, gradually declining and becoming undetectable after 9 h. Recovery from leachate was 45% of the initial fluensulfone applied to the soil surface. In separate experiments, 30-cm-long soil columns were saturated with 1 L of water, and then segregated into three 10-cm sections. Fluensulfone recovery was 41, 34, 29, and 13% in Chualar sandy loam, Arredondo sand, Greenville sandy clay loam, and Tifton loamy sand, respectively, in the top 10-cm section. CONCLUSION: Data indicated that soil organic matter and clay contents will affect sorption, mobility, and dissipation of fluensulfone. © 2017 Society of Chemical Industry.