Zebrafish Caudal Haematopoietic Embryonic Stromal Tissue (CHEST) Cells Support Haematopoiesis.

Haematopoiesis is an essential process in early vertebrate development that occurs in different distinct spatial locations in the embryo that shift over time. These different sites have distinct functions: in some anatomical locations specific hematopoietic stem and progenitor cells (HSPCs) are generated de novo. In others, HSPCs expand. HSPCs differentiate and renew in other locations, ensuring homeostatic maintenance. These niches primarily control haematopoiesis through a combination of cell-to-cell signalling and cytokine secretion that elicit unique biological effects in progenitors. To understand the molecular signals generated by these niches, we report the generation of caudal hematopoietic embryonic stromal tissue (CHEST) cells from 72-hours post fertilization (hpf) caudal hematopoietic tissue (CHT), the site of embryonic HSPC expansion in fish. CHEST cells are a primary cell line with perivascular endothelial properties that expand hematopoietic cells in vitro. Morphological and transcript analysis of these cultures indicates lymphoid, myeloid, and erythroid differentiation, indicating that CHEST cells are a useful tool for identifying molecular signals critical for HSPC proliferation and differentiation in the zebrafish. These findings permit comparison with other temporally and spatially distinct haematopoietic-supportive zebrafish niches, as well as with mammalian haematopoietic-supportive cells to further the understanding of the evolution of the vertebrate hematopoietic system

How do inclusionary and exclusionary autocracies affect ordinary people?

We propose a distinction between inclusionary and exclusionary autocratic ruling strategies and develop novel theoretical propositions on the legacy that these strategies leave on citizens’ political attitudes once the autocratic regime broke down. Using data of 1.3 million survey respondents from 71 countries and hierarchical age–period–cohort models, we estimate between and within cohort differences in citizens’ democratic support. We find that inclusionary regimes—with wider redistribution of socioeconomic and political benefits—leave a stronger antidemocratic legacy than exclusionary regimes on the political attitudes of their citizens. Similarly, citizens who were part of the winning group in an autocracy are more critical with democracy compared with citizens who were part of discriminated groups. This article contributes to our understanding about how autocracies affect the hearts and minds of ordinary citizens

Interferon-γ acutely augments inhibition of neocortical layer 5 pyramidal neurons

BACKGROUND: Interferon-γ (IFN-γ, a type II IFN) is present in the central nervous system (CNS) under various conditions. Evidence is emerging that, in addition to its immunological role, IFN-γ modulates neuronal morphology, function, and development in several brain regions. Previously, we have shown that raising levels of IFN-β (a type I IFN) lead to increased neuronal excitability of neocortical layer 5 pyramidal neurons. Because of shared non-canonical signaling pathways of both cytokines, we hypothesized a similar neocortical role of acutely applied IFN-γ. METHODS: We used semi-quantitative RT-PCR, immunoblotting, and immunohistochemistry to analyze neuronal expression of IFN-γ receptors and performed whole-cell patch-clamp recordings in layer 5 pyramidal neurons to investigate sub- and suprathreshold excitability, properties of hyperpolarization-activated cyclic nucleotide-gated current (Ih), and inhibitory neurotransmission under the influence of acutely applied IFN-γ. RESULTS: We show that IFN-γ receptors are present in the membrane of rat's neocortical layer 5 pyramidal neurons. As expected from this and the putative overlap in IFN type I and II alternative signaling pathways, IFN-γ diminished Ih, mirroring the effect of type I IFNs, suggesting a likewise activation of protein kinase C (PKC). In contrast, IFN-γ did neither alter subthreshold nor suprathreshold neuronal excitability, pointing to augmented inhibitory transmission by IFN-γ. Indeed, IFN-γ increased electrically evoked inhibitory postsynaptic currents (IPSCs) on neocortical layer 5 pyramidal neurons. Furthermore, amplitudes of spontaneous IPSCs and miniature IPSCs were elevated by IFN-γ, whereas their frequency remained unchanged. CONCLUSIONS: The expression of IFN-γ receptors on layer 5 neocortical pyramidal neurons together with the acute augmentation of inhibition in the neocortex by direct application of IFN-γ highlights an additional interaction between the CNS and immune system. Our results strengthen our understanding of the role of IFN-γ in neocortical neurotransmission and emphasize its impact beyond its immunological properties, particularly in the pathogenesis of neuropsychiatric disorders

Protocol for Outcome Evaluation of Ayahuasca-Assisted Addiction Treatment : The Case of Takiwasi Center

The present study describes the protocol for the Ayahuasca Treatment Outcome Project (ATOP) with a special focus on the evaluation of addiction treatment services provided through Takiwasi Center, the first ATOP study site. The goal of the project is to assess treatment outcomes and understand the therapeutic mechanisms of an Ayahuasca-assisted, integrative treatment model for addiction rehabilitation in the Peruvian Amazon. The proposed intervention protocol highlights the significance of treatment setting in the design, delivery, and efficacy of an addiction rehabilitation program that involves the potent psychedelic tea known as Ayahuasca. After describing the context of the study, we put forth details about our mixed-methods approach to data collection and analysis, with which we seek to gain an understanding of why, how, and for whom this specific ayahuasca-assisted treatment program is effective across a range of outcomes. The ATOP protocol employs qualitative research methods as a means to determine which aspects of the setting are meaningful to clients and practitioners, and how this may correlate with outcome measures. This paper delineates the core principles, methods, and measures of the overall ATOP umbrella, then discusses the role of ATOP in the context of the literature on long-term residential programs. To conclude, we discuss the strengths and limitations of the protocol and the intended future of the project

The Grism Lens-Amplified Survey from Space (GLASS). V. Extent and spatial distribution of star formation in z~0.5 cluster galaxies

We present the first study of the spatial distribution of star formation in z~0.5 cluster galaxies. The analysis is based on data taken with the Wide Field Camera 3 as part of the Grism Lens-Amplified Survey from Space (GLASS). We illustrate the methodology by focusing on two clusters (MACS0717.5+3745 and MACS1423.8+2404) with different morphologies (one relaxed and one merging) and use foreground and background galaxies as field control sample. The cluster+field sample consists of 42 galaxies with stellar masses in the range 10^8-10^11 M_sun, and star formation rates in the range 1-20 M_sun/yr. Both in clusters and in the field, H{\alpha} is more extended than the rest-frame UV continuum in 60% of the cases, consistent with diffuse star formation and inside out growth. In ~20% of the cases, the H{\alpha} emission appears more extended in cluster galaxies than in the field, pointing perhaps to ionized gas being stripped and/or star formation being enhanced at large radii. The peak of the H{\alpha} emission and that of the continuum are offset by less than 1 kpc. We investigate trends with the hot gas density as traced by the X-ray emission, and with the surface mass density as inferred from gravitational lens models and find no conclusive results. The diversity of morphologies and sizes observed in H_alpha illustrates the complexity of the environmental process that regulate star formation. Upcoming analysis of the full GLASS dataset will increase our sample size by almost an order of magnitude, verifying and strengthening the inference from this initial dataset.Comment: 18 pages, 15 figures, accepted for publication in Ap

Disparities in Meeting USPSTF Breast, Cervical, and Colorectal Cancer Screening Guidelines Among Women in the United States

Introduction Many sociodemographic factors affect women’s ability to meet cancer screening guidelines. Our objective was to examine which sociodemographic characteristics were associated with women meeting US Preventive Services Task Force (USPSTF) guidelines for breast, cervical, and colorectal cancer screening. Methods We used 2018 Behavioral Risk Factor Surveillance System data to examine the association between sociodemographic variables, such as race/ethnicity, rurality, education, and insurance status, and self-reported cancer screening for breast, cervical, and colorectal cancer. We used multivariable log-binomial regression models to estimate adjusted prevalence ratios and 95% CIs. Results Overall, the proportion of women meeting USPSTF guidelines for breast, cervical, and colorectal cancer screening was more than 70%. The prevalence of meeting screening guidelines was 6% to 10% greater among non-Hispanic Black women than among non-Hispanic White women across all 3 types of cancer screening. Women who lacked health insurance had a 26% to 39% lower screening prevalence across screening types than women with health insurance. Compared with women with $50,000 or more in annual household income, women with less than$50,000 in annual household income had a 3% to 8% lower screening prevalence across all 3 screening types. For colorectal cancer, the prevalence of screening was 7% less among women who lived in rural counties than among women in metropolitan counties. Conclusion Many women still do not meet current USPSTF guidelines for breast, cervical, and colorectal cancer screening. Screening disparities are persistent among socioeconomically disadvantaged groups, especially women with low incomes and without health insurance. To increase the prevalence of cancer screening and reduce disparities, interventions must focus on reducing economic barriers and improving access to care

Spitzer UltRa Faint SUrvey Program (SURFS UP). II. IRAC-Detected Lyman-Break Galaxies at 6 < z < 10 Behind Strong-Lensing Clusters

We study the stellar population properties of the IRAC-detected $6 \lesssim z \lesssim 10$ galaxy candidates from the Spitzer UltRa Faint SUrvey Program (SURFS UP). Using the Lyman Break selection technique, we find a total of 16 new galaxy candidates at $6 \lesssim z \lesssim 10$ with $S/N \geq 3$ in at least one of the IRAC $3.6\mu$m and $4.5\mu$m bands. According to the best mass models available for the surveyed galaxy clusters, these IRAC-detected galaxy candidates are magnified by factors of $\sim 1.2$--$5.5$. We find that the IRAC-detected $6 \lesssim z \lesssim 10$ sample is likely not a homogeneous galaxy population: some are relatively massive (stellar mass as high as $4 \times 10^9\,M_{\odot}$) and evolved (age $\lesssim 500$ Myr) galaxies, while others are less massive ($M_{\text{stellar}}\sim 10^8\,M_{\odot}$) and very young ($\sim 10$ Myr) galaxies with strong nebular emission lines that boost their rest-frame optical fluxes. We identify two Ly$\alpha$ emitters in our sample from the Keck DEIMOS spectra, one at $z_{\text{Ly}\alpha}=6.76$ (in RXJ1347) and one at $z_{\text{Ly}\alpha}=6.32$ (in MACS0454). We show that IRAC $[3.6]-[4.5]$ color, when combined with photometric redshift, can be used to identify galaxies likely with strong nebular emission lines within certain redshift windows.Comment: ApJ in pres

Eosinophils Play a Surprising Leading Role in Recurrent Urticaria in Horses

Urticaria, independent of or associated with allergies, is commonly seen in horses and often shows a high reoccurrence rate. Managing these horses is discouraging, and efficient treatment options are lacking. Due to an incidental finding in a study on horses affected by insect bite hypersensitivity using the eosinophil-targeting eIL-5-CuMV-TT vaccine, we observed the prevention of reoccurring seasonal urticaria in four subsequent years with re-vaccination. In an exploratory case series of horses affected with non-seasonal urticaria, we aimed to investigate the role of eosinophils in urticaria. Skin punch biopsies for histology and qPCR of eosinophil associated genes were performed. Further, two severe, non-seasonal, recurrent urticaria-affected horses were vaccinated using eIL-5-CuMV-TT, and urticaria flare-up was followed up with re-vaccination for several years. Eotaxin-2, eotaxin-3, IL-5, CCR5, and CXCL10 showed high sensitivity and specificity for urticarial lesions, while eosinophils were present in 50% of histological tissue sections. The eIL-5-CuMV-TT vaccine reduced eosinophil counts in blood, cleared clinical signs of urticaria, and even prevented new episodes of urticaria in horses with non-seasonal recurrent urticaria. This indicates that eosinophils play a leading role in urticaria in horses, and targeting eosinophils offers an attractive new treatment option, replacing the use of corticosteroids

Feasibility of Digital Memory Assessments in an Unsupervised and Remote Study Setting

Sensitive and frequent digital remote memory assessments via mobile devices hold the promise to facilitate the detection of cognitive impairment and decline. However, in order to be successful at scale, cognitive tests need to be applicable in unsupervised settings and confounding factors need to be understood. This study explored the feasibility of completely unsupervised digital cognitive assessments using three novel memory tasks in a Citizen Science project across Germany. To that end, the study aimed to identify factors associated with stronger participant retention, to examine test-retest reliability and the extent of practice effects, as well as to investigate the influence of uncontrolled settings such as time of day, delay between sessions or screen size on memory performance. A total of 1,407 adults (aged 18-89) participated in the study for up to 12 weeks, completing weekly memory tasks in addition to short questionnaires regarding sleep duration, subjective cognitive complaints as well as cold symptoms. Participation across memory tasks was pseudorandomized such that individuals were assigned to one of three memory paradigms resulting in three otherwise identical sub-studies. One hundred thirty-eight participants contributed to two of the three paradigms. Critically, for each memory task 12 independent parallel test sets were used to minimize effects of repeated testing. First, we observed a mean participant retention time of 44 days, or 4 active test sessions, and 77.5% compliance to the study protocol in an unsupervised setting with no contact between participants and study personnel, payment or feedback. We identified subject-level factors that contributed to higher retention times. Second, we found minor practice effects associated with repeated cognitive testing, and reveal evidence for acceptable-to-good retest reliability of mobile testing. Third, we show that memory performance assessed through repeated digital assessments was strongly associated with age in all paradigms, and individuals with subjectively reported cognitive decline presented lower mnemonic discrimination accuracy compared to non-complaining participants. Finally, we identified design-related factors that need to be incorporated in future studies such as the time delay between test sessions. Our results demonstrate the feasibility of fully unsupervised digital remote memory assessments and identify critical factors to account for in future studies

Synergistic Biophysical Techniques Reveal Structural Mechanisms of Engineered Cationic Antimicrobial Peptides in Lipid Model Membranes

In the quest for new antibiotics, two novel engineered cationic antimicrobial peptides (eCAPs) have been rationally designed. WLBU2 and D8 (all 8 valines are the d-enantiomer) efficiently kill both Gram-negative and -positive bacteria, but WLBU2 is toxic and D8 nontoxic to eukaryotic cells. We explore protein secondary structure, location of peptides in six lipid model membranes, changes in membrane structure and pore evidence. We suggest that protein secondary structure is not a critical determinant of bactericidal activity, but that membrane thinning and dual location of WLBU2 and D8 in the membrane headgroup and hydrocarbon region may be important. While neither peptide thins the Gram-negative lipopolysaccharide outer membrane model, both locate deep into its hydrocarbon region where they are primed for self-promoted uptake into the periplasm. The partially α-helical secondary structure of WLBU2 in a red blood cell (RBC) membrane model containing 50 % cholesterol, could play a role in destabilizing this RBC membrane model causing pore formation that is not observed with the D8 random coil, which correlates with RBC hemolysis caused by WLBU2 but not by D8.Fil: Heinrich, Frank. University of Carnegie Mellon; Estados UnidosFil: Salyapongse, Aria. University of Carnegie Mellon; Estados UnidosFil: Kumagai, Akari. University of Carnegie Mellon; Estados UnidosFil: Dupuy, Fernando Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Shukla, Karpur. University of Carnegie Mellon; Estados UnidosFil: Penk, Anja. Universitat Leipzig; AlemaniaFil: Huster, Daniel. Universitat Leipzig; AlemaniaFil: Ernst, Robert K.. University of Maryland; Estados UnidosFil: Pavlova, Anna. Georgia Institute Of Techology. School Of Chemical & Biomolecular Engineering; Estados UnidosFil: Gumbart, James C.. Georgia Institute Of Techology. School Of Chemical & Biomolecular Engineering; Estados UnidosFil: Deslouches, Berthony. University of Pittsburgh; Estados UnidosFil: Di, Y. Peter. University of Pittsburgh; Estados UnidosFil: Tristram-Nagle, Stephanie. University of Carnegie Mellon; Estados Unido