Exploring the Cosmic Reionization Epoch in Frequency Space: An Improved Approach to Remove the Foreground in 21 cm Tomography

Aiming to correctly restore the redshifted 21 cm signals emitted by the neutral hydrogen during the cosmic reionization processes, we re-examine the separation approaches based on the quadratic polynomial fitting technique in frequency space to investigate whether they works satisfactorily with complex foreground, by quantitatively evaluate the quality of restored 21 cm signals in terms of sample statistics. We construct the foreground model to characterize both spatial and spectral substructures of the real sky, and use it to simulate the observed radio spectra. By comparing between different separation approaches through statistical analysis of restored 21 cm spectra and corresponding power spectra, as well as their constraints on the mean halo bias $b$ and average ionization fraction $x_e$ of the reionization processes, at $z=8$ and the noise level of 60 mK we find that, although the complex foreground can be well approximated with quadratic polynomial expansion, a significant part of Mpc-scale components of the 21 cm signals (75% for $\gtrsim 6h^{-1}$ Mpc scales and 34% for $\gtrsim 1h^{-1}$ Mpc scales) is lost because it tends to be mis-identified as part of the foreground when single-narrow-segment separation approach is applied. The best restoration of the 21 cm signals and the tightest determination of $b$ and $x_e$ can be obtained with the three-narrow-segment fitting technique as proposed in this paper. Similar results can be obtained at other redshifts.Comment: 33 pages, 14 figures. Accepted for publication in Ap

Practitioner perspectives on the use of acceptance and commitment therapy for bereavement support:A qualitative study

Background: There is currently a high demand for bereavement support coupled with inconclusive findings as to the efficacy of existing approaches. Acceptance and Commitment Therapy (ACT) aims to improve human functioning and has shown efficacy across a wide range of conditions. ACT may be a promising means of supporting bereaved people, yet evidence on the use of ACT for bereavement support is lacking. The aim of this study is to explore how ACT is currently used for bereavement support and practitioner perspectives of how it helps following bereavement. Methods: Semi-structured interviews were conducted online via MS Teams with practitioners experienced in using ACT for bereavement support. Data were analysed thematically guided by a framework approach. Results: Nine participants were recruited. Three themes were identified: (i) creating psychological space around grief; (ii) using psychological space for value-directed action in the midst of grieving, and (iii) adapting ACT for bereavement support. Practitioners indicated that ACT improves clients’ relationship with distressing internal experiences. Metaphors and mindfulness techniques were used to encourage acceptance of grief responses, taking perspective on distressing thoughts and images, and contact with the present moment. Better relationships with distressing experiences were regarded as less psychologically taxing, improving coping and well-being, while providing the psychological space to engage in value-directed action. Values exploration, sometimes using metaphors and exercises, was seen as supporting the bereaved person to rediscover a sense of purpose and engage in meaningful activities alongside their grief. Practitioners used ACT flexibly, integrating other interventions, and adapted ACT to the perceived sensitivities of bereaved people, and age-related and developmental factors.Conclusion: ACT is used to support people who have been bereaved to live effectively with the difficult thoughts and feelings associated with grieving and to enable them to gradually identify, reconnect with, and act in line with their values after loss. Keywords: Acceptance and commitment therapy, ACT, bereavement, grief, qualitative research, psychological adaptation, coping skills, coping behaviour, coping strategies, psychological well-being<br/

Human-induced intensification of terrestrial water cycle in dry regions of the globe

Anthropogenic climate change (ACC) strengthens the global terrestrial water cycle (TWC) through increases in annual total precipitation (PRCPTOT) over global land. While the increase in the average global terrestrial PRCPTOT has been attributed to ACC, it is unclear whether this is equally true in dry and wet regions, given the difference in PRCPTOT changes between the two climatic regions. Here, we show the increase in PRCPTOT in dry regions is twice as fast as in wet regions of the globe during 1961–2018 in both observations and simulations. This faster increase is projected to grow with future warming, with an intensified human-induced TWC in the driest regions of the globe. We show this phenomenon can be explained by the faster warming and precipitation response rates as well as the stronger moisture transport in dry regions under ACC. Quantitative detection and attribution results show that the global increase in PRCPTOT can no longer be attributed to ACC if dry regions are excluded. From 1961–2018, the observed PRCPTOT increased by 5.63%~7.39% (2.44%~2.80%) over dry (wet) regions, and as much as 89% (as little as 5%) can be attributed to ACC. The faster ACC-induced TWC in dry regions is likely to have both beneficial and detrimental effects on dry regions of the globe, simultaneously alleviating water scarcity while increasing the risk of major flooding

Pathways to clinical CLARITY: volumetric analysis of irregular, soft, and heterogeneous tissues in development and disease

AbstractThree-dimensional tissue-structural relationships are not well captured by typical thin-section histology, posing challenges for the study of tissue physiology and pathology. Moreover, while recent progress has been made with intact methods for clearing, labeling, and imaging whole organs such as the mature brain, these approaches are generally unsuitable for soft, irregular, and heterogeneous tissues that account for the vast majority of clinical samples and biopsies. Here we develop a biphasic hydrogel methodology, which along with automated analysis, provides for high-throughput quantitative volumetric interrogation of spatially-irregular and friable tissue structures. We validate and apply this approach in the examination of a variety of developing and diseased tissues, with specific focus on the dynamics of normal and pathological pancreatic innervation and development, including in clinical samples. Quantitative advantages of the intact-tissue approach were demonstrated compared to conventional thin-section histology, pointing to broad applications in both research and clinical settings.</jats:p

Expansion and conversion of human pancreatic ductal cells into insulin-secreting endocrine cells

Pancreatic islet β-cell insufficiency underlies pathogenesis of diabetes mellitus; thus, functional β-cell replacement from renewable sources is the focus of intensive worldwide effort. However, in vitro production of progeny that secrete insulin in response to physiological cues from primary human cells has proven elusive. Here we describe fractionation, expansion and conversion of primary adult human pancreatic ductal cells into progeny resembling native β-cells. FACS-sorted adult human ductal cells clonally expanded as spheres in culture, while retaining ductal characteristics. Expression of the cardinal islet developmental regulators Neurog3, MafA, Pdx1 and Pax6 converted exocrine duct cells into endocrine progeny with hallmark β-cell properties, including the ability to synthesize, process and store insulin, and secrete it in response to glucose or other depolarizing stimuli. These studies provide evidence that genetic reprogramming of expandable human pancreatic cells with defined factors may serve as a general strategy for islet replacement in diabetes. DOI: http://dx.doi.org/10.7554/eLife.00940.00

High blood galectin-3 level associated with risk of frailty in aging

BackgroundFrailty is one of the most problematic expressions of population aging, but its underlying mechanism has not been fully elucidated. Circulating galectin-3 (Gal-3) is involved in the pathogenesis of many age-related diseases. This study aims to explore the influence of circulating Gal-3 on the regulation of frailty and aging and to identify the potential mechanism further.MethodsIn this cross-sectional analysis, the Fried frailty phenotype (FP) was assessed among 149 community elderly residents in Shanghai. Peripheral blood mononuclear cells (PBMCs) were isolated by the Ficoll-Paque density gradient method, and differentially expressed genes (DEGs) encoding transcription factors in frailty were detected by Illumina and bioinformatics analyzed with R software. Gene Ontology (GO) enrichment analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to explore the functional roles of these DEGs and the target genes related to frailty phenotypes. The serum Gal-3 concentration was tested by enzyme-linked immunosorbent assay (ELISA). Mouse frailty phenotype was used to construct an in vivo model of frailty, after which the serum levels of circulating Gal-3 and its gene expression levels in mouse tissues were determined.ResultsParticipants’ mean age was 72.04 ± 7.05 years. In total, 21.48% were frail and 36.91% were pre-frail. The mean serum Gal-3 concentration was 46.34 ± 17.99 ng/mL in frail participants, 32.30 ± 8.14 ng/mL in pre-frail participants, and 26.00 ± 5.87 ng/mL in non-frail individuals (p &lt; 0.001). Significant positive correlations between serum Gal-3 level and FP score, SARC-F score, C-reactive protein (CRP), interleukin-6, etc., were observed. In addition, the KEGG pathway and GO enrichment analyses showed that 265 DEGs in PBMCs of frail participants were mainly related to inflammatory response, translation, RNA binding, protein binding, ribosome, and primary immunodeficiency. LGALS3 was identified as the overlapping gene between frailty-related DEGs and aging-related DEGs. The elevated serum Gal-3 concentration in the in vivo model of frailty was consistent with the results in participants.ConclusionIn both community-dwelling older adults and aged mice, serum Gal-3 concentration was positively correlated with frailty. This circulating mediator may be a promising indicator of frailty.Clinical trial registrationChinese Clinical Trial Registry identifier, ChiCTR2000036399

Comparative analysis of liver transcriptome reveals adaptive responses to hypoxia environmental condition in Tibetan chicken

Objective Tibetan chickens, which have unique adaptations to extreme high-altitude environments, exhibit phenotypic and physiological characteristics that are distinct from those of lowland chickens. However, the mechanisms underlying hypoxic adaptation in the liver of chickens remain unknown. Methods RNA-sequencing (RNA-Seq) technology was used to assess the differentially expressed genes (DEGs) involved in hypoxia adaptation in highland chickens (native Tibetan chicken [HT]) and lowland chickens (Langshan chicken [LS], Beijing You chicken [BJ], Qingyuan Partridge chicken [QY], and Chahua chicken [CH]). Results A total of 352 co-DEGs were specifically screened between HT and four native lowland chicken breeds. Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses indicated that these co-DEGs were widely involved in lipid metabolism processes, such as the peroxisome proliferator-activated receptors (PPAR) signaling pathway, fatty acid degradation, fatty acid metabolism and fatty acid biosynthesis. To further determine the relationship from the 352 co-DEGs, protein-protein interaction network was carried out and identified eight genes (ACSL1, CPT1A, ACOX1, PPARC1A, SCD, ACSBG2, ACACA, and FASN) as the potential regulating genes that are responsible for the altitude difference between the HT and other four lowland chicken breeds. Conclusion This study provides novel insights into the molecular mechanisms regulating hypoxia adaptation via lipid metabolism in Tibetan chickens and other highland animals

Conditional Expression of Smad7 in Pancreatic β Cells Disrupts TGF-β Signaling and Induces Reversible Diabetes Mellitus

Identification of signaling pathways that maintain and promote adult pancreatic islet functions will accelerate our understanding of organogenesis and improve strategies for treating diseases like diabetes mellitus. Previous work has implicated transforming growth factor-β (TGF-β) signaling as an important regulator of pancreatic islet development, but has not established whether this signaling pathway is required for essential islet functions in the adult pancreas. Here we describe a conditional system for expressing Smad7, a potent inhibitor of TGF-β signaling, to identify distinct roles for this pathway in adult and embryonic β cells. Smad7 expression in Pdx1 (+) embryonic pancreas cells resulted in striking embryonic β cell hypoplasia and neonatal lethality. Conditional expression of Smad7 in adult Pdx1 (+) cells reduced detectable β cell expression of MafA, menin, and other factors that regulate β cell function. Reduced pancreatic insulin content and hypoinsulinemia produced overt diabetes that was fully reversed upon resumption of islet TGF-β signaling. Thus, our studies reveal that TGF-β signaling is crucial for establishing and maintaining defining features of mature pancreatic β cells