Thousands of eukaryotic protein-coding genes are noncanonically spliced to produce circular RNAs. Bioinformatics has indicated that long introns generally flank exons that circularize in Drosophila, ...but the underlying mechanisms by which these circular RNAs are generated are largely unknown. Here, using extensive mutagenesis of expression plasmids and RNAi screening, we reveal that circularization of the Drosophila laccase2 gene is regulated by both intronic repeats and trans-acting splicing factors. Analogous to what has been observed in humans and mice, base-pairing between highly complementary transposable elements facilitates backsplicing. Long flanking repeats (∼ 400 nucleotides nt) promote circularization cotranscriptionally, whereas pre-mRNAs containing minimal repeats (<40 nt) generate circular RNAs predominately after 3' end processing. Unlike the previously characterized Muscleblind (Mbl) circular RNA, which requires the Mbl protein for its biogenesis, we found that Laccase2 circular RNA levels are not controlled by Mbl or the Laccase2 gene product but rather by multiple hnRNP (heterogeneous nuclear ribonucleoprotein) and SR (serine-arginine) proteins acting in a combinatorial manner. hnRNP and SR proteins also regulate the expression of other Drosophila circular RNAs, including Plexin A (PlexA), suggesting a common strategy for regulating backsplicing. Furthermore, the laccase2 flanking introns support efficient circularization of diverse exons in Drosophila and human cells, providing a new tool for exploring the functional consequences of circular RNA expression across eukaryotes.
Climate drivers such as humidity and temperature may play a key role in influenza seasonal transmission dynamics. Such a relationship has been well defined for temperate regions. However, to date no ...models capable of capturing the diverse seasonal pattern in tropical and subtropical climates exist. In addition, multiple influenza viruses could cocirculate and shape epidemic dynamics. Here we construct seven mechanistic epidemic models to test the effect of two major climate drivers (humidity and temperature) and multi-strain co-circulation on influenza transmission in Hong Kong, an influenza epidemic center located in the subtropics. Based on model fit to long-term influenza surveillance data from 1998 to 2018, we found that a simple model incorporating the effect of both humidity and temperature best recreated the influenza epidemic patterns observed in Hong Kong. The model quantifies a bimodal effect of absolute humidity on influenza transmission where both low and very high humidity levels facilitate transmission quadratically; the model also quantifies the monotonic but nonlinear relationship with temperature. In addition, model results suggest that, at the population level, a shorter immunity period can approximate the co-circulation of influenza virus (sub)types. The basic reproductive number R0 estimated by the best-fit model is also consistent with laboratory influenza survival and transmission studies under various combinations of humidity and temperature levels. Overall, our study has developed a simple mechanistic model capable of quantifying the impact of climate drivers on influenza transmission in (sub)tropical regions. This model can be applied to improve influenza forecasting in the (sub)tropics in the future.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Females have a greater immunological advantage than men, yet they are more prone to autoimmune disorders. The basis for this sex bias lies in the X chromosome, which contains many immunity-related ...genes. Femalemammals use X chromosome inactivation (XCI) to generate a transcriptionally silent inactive X chromosome (Xi) enriched with heterochromatic modifications and XIST/Xist RNA, which equalizes gene expression between the sexes. Here, we examine the maintenance of XCI in lymphocytes from females in mice and humans. Strikingly, we find that mature naïve T and B cells have dispersed patterns of XIST/Xist RNA, and they lack the typical heterochromatic modifications of the Xi. In vitro activation of lymphocytes triggers the return of XIST/Xist RNA transcripts and some chromatin marks (H3K27me3, ubiquitin-H2A) to the Xi. Single-cell RNA FISH analysis of female T cells revealed that the X-linked immunity genes CD40LG and CXCR3 are biallelically expressed in some cells. Using knockout and knockdown approaches, we find that Xist RNA-binding proteins, YY1 and hnRNPU, are critical for recruitment of XIST/Xist RNA back to the Xi. Furthermore, we examined B cells from patients with systemic lupus erythematosus, an autoimmune disorder with a strong female bias, and observed different XIST RNA localization patterns, evidence of biallelic expression of immunity-related genes, and increased transcription of these genes. We propose that the Xi in female lymphocytes is predisposed to become partially reactivated and to overexpress immunity-related genes, providing the first mechanistic evidence to our knowledge for the enhanced immunity of females and their increased susceptibility for autoimmunity.
Cardiovascular disease is an inflammatory disorder characterized by the progressive formation of plaque in coronary arteries, termed atherosclerosis. It is a multifactorial disease that is one of the ...leading causes of death worldwide. Although a number of risk factors have been associated with disease progression, the underlying inflammatory mechanisms contributing to atherosclerosis remain to be fully delineated. Within the last decade, the potential role for infection in inflammatory plaque progression has received considerable interest. Microbial pathogens associated with periodontal disease have been of particular interest due to the high levels of bacteremia that are observed after routine dental procedures and every day oral activities, such as tooth brushing. Here, we explore the potential mechanisms that may explain how periodontal pathogens either directly or indirectly elicit immune dysregulation and consequently progressive inflammation manifested as atherosclerosis. Periodontal pathogens have been shown to contribute directly to atherosclerosis by disrupting endothelial cell function, one of the earliest indicators of cardiovascular disease. Oral infection is thought to indirectly induce elevated production of inflammatory mediators in the systemic circulation. Recently, a number of studies have been conducted focusing on how disruption of the gut microbiome influences the systemic production of proinflammatory cytokines and consequently exacerbation of inflammatory diseases such as atherosclerosis. It is clear that the immune mechanisms leading to atherosclerotic plaque progression, by oral infection, are complex. Understanding the immune pathways leading to disease progression is essential for the future development of anti‐inflammatory therapies for this chronic disease.
Accurate forecasts of influenza incidence can be used to inform medical and public health decision-making and response efforts. However, forecasting systems are uncommon in most countries, with a few ...notable exceptions. Here we use publicly available data from the World Health Organization to generate retrospective forecasts of influenza peak timing and peak intensity for 64 countries, including 18 tropical and subtropical countries. We find that accurate and well-calibrated forecasts can be generated for countries in temperate regions, with peak timing and intensity accuracy exceeding 50% at four and two weeks prior to the predicted epidemic peak, respectively. Forecasts are significantly less accurate in the tropics and subtropics for both peak timing and intensity. This work indicates that, in temperate regions around the world, forecasts can be generated with sufficient lead time to prepare for upcoming outbreak peak incidence.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose
There is a strong need to improve the prognostication of breast cancer patients in order to prevent over- and undertreatment, especially when considering adjuvant chemotherapy. Tumour stroma ...characteristics might be valuable in predicting disease progression.
Methods
Studies regarding the prognostic value of tumour–stroma ratio (TSR) in breast cancer are evaluated.
Results
A high stromal content is related to a relatively poor prognosis. The most pronounced prognostic effect of this parameter seems to be observed in the triple-negative breast cancer (TNBC) subtype.
Conclusions
TSR assessment might represent a simple, fast and reproducible prognostic factor at no extra costs, and could possibly be incorporated into routine pathological diagnostics. Despite these advantages, a robust clinical validation of this parameter has yet to be established in prospective studies.
We present EMPIRE, an IRAM 30 m large program that mapped λ = 3-4 mm dense gas tracers at ∼1-2 kpc resolution across the whole star-forming disk of nine nearby massive spiral galaxies. We describe ...the EMPIRE observing and reduction strategies and show new whole-galaxy maps of HCN(1−0), HCO+(1−0), HNC(1−0), and CO(1−0). We explore how the HCN-to-CO and IR-to-HCN ratios, observational proxies for the dense gas fraction and dense gas star formation efficiency, depend on host galaxy and local environment. We find that the fraction of dense gas correlates with stellar surface density, gas surface density, molecular-to-atomic gas ratio, and dynamical equilibrium pressure. In EMPIRE, the star formation rate per unit dense gas is anticorrelated with these same environmental parameters. Thus, although dense gas appears abundant in the central regions of many spiral galaxies, this gas appears relatively inefficient at forming stars. These results qualitatively agree with previous work on nearby galaxies and the Milky Way's Central Molecular Zone. To first order, EMPIRE demonstrates that the conditions in a galaxy disk set the gas density distribution and that the dense gas traced by HCN shows an environment-dependent relation to star formation. However, our results also show significant ( 0.2 dex) galaxy-to-galaxy variations. We suggest that gas structure below the scale of our observations and dynamical effects likely also play an important role.
Aims. We observationally investigate the relation between the photoelectric heating efficiency in photodissociation regions (PDRs) and the charge of polycyclic aromatic hydrocarbons (PAHs), which are ...considered to play a key role in photoelectric heating. Methods. Using PACS onboard Herschel, we observed six PDRs spanning a wide range of far-ultraviolet radiation fields (G0 = 100−105). To measure the photoelectric heating efficiency, we obtained the intensities of the main cooling lines in these PDRs, i.e., the O i 63 μm, 145 μm, and C ii 158 μm, as well as the far-infrared (FIR) continuum intensity. We used Spitzer/IRS spectroscopic mapping observations to investigate the mid-infrared (MIR; 5.5−14 μm) PAH features in the same regions. We decomposed the MIR PAH emission into that of neutral (PAH0) and positively ionized (PAH+) species to derive the fraction of the positively charged PAHs in each region, and compare it to the photoelectric heating efficiency. Results. The heating efficiency traced by (O i 63 μm + O i 145 μm + C ii 158 μm)/TIR, where TIR is the total infrared flux, ranges between 0.1% and 0.9% in different sources, and the fraction of PAH+ relative to (PAH0+ PAH+) spans from 0 (+11)% to 87 (±10)%. All positions with a high PAH+ fraction show a low heating efficiency, and all positions with a high heating efficiency have a low PAH+ fraction, supporting the scenario in which a positive grain charge results in a decreased heating efficiency. Theoretical estimates of the photoelectric heating efficiency show a stronger dependence on the charging parameter γ = G0T1/2/ne than the observed efficiency reported in this study, and the discrepancy is significant at low γ. The photoelectric heating efficiency on PAHs, traced by (O i 63 μm + O i 145 μm + C ii 158 μm)/(PAH-band emission + O i 63 μm + O i 145 μm + C ii 158 μm), shows a much better match between the observations and the theoretical estimates. Conclusions. The good agreement of the photoelectric heating efficiency on PAHs with a theoretical model indicates the dominant contribution of PAHs to the photoelectric heating. This study demonstrates the fundamental role that PAHs have in photoelectric heating. More studies of their charging behavior are crucial to understand the thermal balance of the interstellar medium.
Carbon Criminals, Climate Crimes analyzes the looming threats posed by climate change from a criminological perspective. It advances the field of green criminology through a examination of the ...criminal nature of catastrophic environmental harms resulting from the release of greenhouse gases. The book describes and explains what corporations in the fossil fuel industry, the U.S. government, and the international political community did, or failed to do, in relation to global warming. Carbon Criminals, Climate Crimes integrates research and theory from a wide variety of disciplines, to analyze four specific state-corporate climate crimes: continued extraction of fossil fuels and rising carbon emissions; political omission (failure) related to the mitigation of these emissions; socially organized climate change denial; and climate crimes of empire, which include militaristic forms of adaptation to climate disruption. The final chapter reviews policies that could mitigate greenhouse gas emissions, adapt to a warming world, and achieve climate justice.
Probiotics, Nutrition, and the Small Intestine Judkins, Taylor C.; Archer, Douglas L.; Kramer, Dean C. ...
Current gastroenterology reports,
2020/1, Letnik:
22, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Purpose of Review
Probiotics are promising remedial treatments for symptoms of small intestine (SI) diseases and promoters of overall good health. Probiotics play an important role in supporting a ...healthy SI microbiome (eubiosis), and in preventing establishment of unhealthy microbiota. SI eubiosis promotes optimal nutrient uptake, and optimal nutritional status maintains a healthy SI, reducing the likelihood of SI diseases. It is important to understand the advantages and limitations of probiotic therapies.
Recent Findings
Microbial dysbiosis decreases the capacity of the small bowel to utilize and absorb dietary compounds. In some studies, probiotic supplements containing lactic acid bacteria and
Bifidobacterium
have been demonstrated effective in supporting beneficial microbes in the SI while improving barrier integrity and reducing nutrient malabsorption and SI disease-related pathology.
Summary
Strain-specific probiotic therapy may be a natural and effective approach to restoring SI barrier integrity and eubiosis, resulting in improved nutrient absorption and better health, including reducing the incidence of and severity of SI diseases.
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