Miracle-dz/UniFAR-FTUs huggingface dataset:
PAXIP1 and STAG2 converge to maintain 3D genome architecture and facilitate promoter/enhancer contacts to enable stress hormone-dependent transcription

Abstract How steroid hormone receptors (SHRs) regulate transcriptional activity remains partly understood. Upon activation, SHRs bind the genome together with a co-regulator repertoire, crucial to induce gene expression. However, it remains unknown which components of the SHR-recruited co-regulator complex are essential to drive transcription following hormonal stimuli. Through a FACS-based genome-wide CRISPR screen, we functionally dissected the Glucocorticoid Receptor (GR) complex. We describe a functional cross-talk between PAXIP1 and the cohesin subunit STAG2, critical for regulation of gene expression by GR. Without altering the GR cistrome, PAXIP1 and STAG2 depletion alter the GR transcriptome, by impairing the recruitment of 3D-genome organization proteins to the GR complex. Importantly, we demonstrate that PAXIP1 is required for stability of cohesin on chromatin, its localization to GR-occupied sites, and maintenance of enhancer-promoter interactions. In lung cancer, where GR acts as tumor suppressor, PAXIP1/STAG2 loss enhances GR-mediated tumor suppressor activity by modifying local chromatin interactions. All together, we introduce PAXIP1 and STAG2 as novel co-regulators of GR, required to maintain 3D-genome architecture and drive the GR transcriptional programme following hormonal stimuli.
Boldine modulates glial transcription and functional recovery in a murine model of contusion spinal cord injury

Membrane channels such as connexins (Cx), pannexins (Panx) and P2X7 receptors (P2X7R) are permeable to calcium ions and other small molecules such as ATP and glutamate. Release of ATP and glutamate through these channels is a key mechanism driving tissue response to traumas such as spinal cord injury (SCI). Boldine, an alkaloid isolated from the Chilean boldo tree, blocks both Cx hemichannels (HC) and Panx. To test if boldine could improve function after SCI, boldine or vehicle was administered to treat mice with a moderate severity contusion-induced SCI. Boldine led to greater spared white matter and increased locomotor function as determined by the Basso Mouse Scale and horizontal ladder rung walk tests. Boldine treatment reduced immunostaining for markers of activated microglia (Iba1) and astrocytic (GFAP) markers while increasing that for axon growth and neuroplasticity (GAP-43). Cell culture studies demonstrated that boldine blocked glial HC, specifically Cx26 and Cx30, in cultured astrocytes and blocked calcium entry through activated P2X7R. RT-qPCR studies showed that boldine treatment reduced expression of the chemokine Ccl2, cytokine IL-6 and microglial gene CD68, while increasing expression of the neurotransmission genes Snap25 and Grin2b, and Gap-43. Bulk RNA sequencing (of the spinal cord revealed that boldine modulated a large number of genes involved in neurotransmission in in spinal cord tissue just below the lesion epicenter at 14 days after SCI. Numbers of genes regulated by boldine was much lower at 28 days after injury. These results indicate that boldine treatment ameliorates injury and spares tissue to increase locomotor function.
Folding : A Parametric Model To Support The Creative Stage Of Architectural Project

Abstract The use of architectural concepts in the designing of a project requires a combination of efforts; theoretical models are lacking in both substance and flexibility. This paper focuses on a parametric model, which has its foundation in contemporary society of information systems. This process gives structure to the decision making which then allows the creative stage of the project to occur. The process of architectural concept is subject of many studies in the field of science of drawing, or in cognitive science or informatics. Its wealth is based on its complexity and the variety of operating conditions that include during its progress. For our purposes, we will focus on the early stages of the project, the moments of conceptual research from which will flow throughout the design approach. This step is the founder of the architectural concept activity is largely associated with the creative dimension. We propose that this model will validate reconstructing the concrete steps of morphogenesis of reference objects. Then we will use the parametric model in a dedicated tool for architectural design. Our choice fell on this issue because the interactivity between the parts is a catalyst for a series of elements that helps the design process by raising the quality and operational modalities of this, creating a real "new aesthetic"
Compressibility of the Quark Stars in Einstein-Gauss-Bonnet Gravity

To study the behavior of some of the quark stars (QSs) in the Einstein-GaussBonnet gravity, we develop analytically the equation of state (EoS). We show that the Gauss-Bonnet coupling affects the star compressibility. This last relates the radial pressure with the thermodynamic volume and analyzes their behavior through the quark stars. We have found that the TOV equation is well behaved as the van der Waals equation. We discuss the characteristics of the radial and tangential compressibility in the surface and inside the star. We have determined the thickness of the region that contains the quarks in the QS. We show that the quark fluid exists in the region between the Schwarzschild radius and the radius of stars. We study the stability under radial and tangential perturbations.
Gravity Modeling in Fold-Thrust Belts: An Example from the Peloritani Mountains, Southern Italy

Laboratory measurement of density values of representative crystalline rocks of the Peloritani Mountains, southern Italy, constrain the interpretation of gravity data collected along a profile from the Tyrrhenian Sea to the Mt. Etna volcano. These data contribute detail to crustal models of this section of the southern Italy orogenic system. Regional gravity modeling, constrained by new petrophysical data, yields the following conclusions: (1) existence of a southward-transported nappe belt of a more internal domain; (2) interpretation of the Taormina tectonic line as the morphological evidence of the thrusting of the Kabilo-Calabrian terrane over the Apenninian-Maghrebian units; (3) reconstruction of the Moho geometry along the geotransect, confirming the abrupt change in depth just starting from the Tyrrhenian coastal zone of Sicily.
The North American summer Arctic front during 1948–2007

Boundaries between air masses, frontal zones, are associated with vegetation boundaries. Using gridded climate reanalysis data, we analyse the air masses and frontal zones of North America in relation to the atmospheric circulation and vegetation productivity. The position of the July Arctic front varies significantly through the period 1948–2007, with a mean position similar to that found by Bryson (1966). The variability of the frontal position can be associated with changes in the general circulation; when the Arctic Oscillation (AO) and Southern Oscillation Index (SOI) are positive (negative), the position of the July Arctic front is further north (south). There is also more spatial variability in the July Arctic frontal position in eastern versus western North America. The location of the frontal zone affects the vegetation through impacts on vegetative production; when the July Arctic front is north (south) of the mean position, the boreal forest and tundra vegetation is more (less) productive. Contrary to other studies that have identified changes in air mass frequency distributions and properties in several regions in response to global warming, we could not find clear evidence of significant changes in the position of the Arctic front in recent years. Copyright © 2009 Royal Meteorological Society
Protection of second booster vaccinations and prior infection against SARS-CoV-2 in the UK SIREN healthcare worker cohort

Background The protection of fourth dose mRNA vaccination against SARS-CoV-2 is relevant to current global policy decisions regarding ongoing booster roll-out. We estimate the effect of fourth dose vaccination, prior infection, and duration of PCR positivity in a highly-vaccinated and largely prior-COVID-19 infected cohort of UK healthcare workers. Methods Participants underwent fortnightly PCR and regular antibody testing for SARS-CoV-2 and completed symptoms questionnaires. A multi-state model was used to estimate vaccine effectiveness (VE) against infection from a fourth dose compared to a waned third dose, with protection from prior infection and duration of PCR positivity jointly estimated. Results 1,298 infections were detected among 9,560 individuals under active follow-up between September 2022 and March 2023. Compared to a waned third dose, fourth dose VE was 13.1% (95%CI 0.9 to 23.8) overall; 24.0% (95%CI 8.5 to 36.8) in the first two months post-vaccination, reducing to 10.3% (95%CI -11.4 to 27.8) and 1.7% (95%CI -17.0 to 17.4) at 2-4 and 4-6 months, respectively. Relative to an infection >2 years ago and controlling for vaccination, 63.6% (95%CI 46.9 to 75.0) and 29.1% (95%CI 3.8 to 43.1) greater protection against infection was estimated for an infection within the past 0-6, and 6-12 months, respectively. A fourth dose was associated with greater protection against asymptomatic infection than symptomatic infection, whilst prior infection independently provided more protection against symptomatic infection, particularly if the infection had occurred within the previous 6 months. Duration of PCR positivity was significantly lower for asymptomatic compared to symptomatic infection. Conclusions Despite rapid waning of protection, vaccine boosters remain an important tool in responding to the dynamic COVID-19 landscape; boosting population immunity in advance of periods of anticipated pressure, such as surging infection rates or emerging variants of concern. Funding UK Health Security Agency, Medical Research Council, NIHR HPRU Oxford, and others.
Geography of Phocid Evolution

Ray, C. E. (Department of Paleobiology, Smithsonian Institution, Washington, D. C. 20560) 1976. Geography of Phocid Evolution. Syst. Zool. 25:391-406. -Phocid distribution suggests origin in and primary radiation from the North Atlantic-Paratethyan region. Phocines and monachines are equally old groups, known first from the lower middle Miocene Calvert Formation. Phocines dominated Paratethys in semi-isolation. Both groups dispersed freely around the margins of the North Atlantic in Miocene and Pliocene time. Phocines entered the North Pacific, probably from the north, in Pliocene time, and have modernized and radiated in latest Cenozoic time, exclusively in the cold waters of the northern hemisphere. Monachine distribution receded southward in the North Atlantic during latest Cenozoic time, and in the Pliocene they spread into both the southern hemisphere, where they radiated in the empty Antarctic, and into the Pacific via the middle American seaway. At least four forces acting independently over the past decade or so combine now to make a fresh look at the geography of marine mammals and its interplay with their systematics rewarding: 1. ITe revitalization of paleogeography resulting from the new dynamism in concepts of crustal evolution. Plate tectonics and sea floor spreading are a general theme in geology today, but most of us in the United States who finished our formal schooling as little as 15 years ago were reared scholastically on the supposedly solid foundation of stable continents, with at most a dutiful if not derisive bow toward continental drift, followed by quick dismissal. The impact of colliding continents is now being felt throughout geology. 2. The development of a cosmopolitan time frame for the Cenozoic Era, through long distance correlation by planktonic foraminifera and nannoplankton, and by magnetic and radiometric techniques. The integration of these lines of evidence, with increasingly rigorous application of stratigraphic principles, has provided a comprehensive working hypothesis against which the fit of patterns of marine mammal relationships may be
Longitudinal associations of sustained low or high income and income variability with incident cardiovascular disease in individuals with type 2 diabetes: a retrospective population-based cohort study

Background and Aims: Longitudinal change in income is crucial in explaining cardiovascular health inequalities, but there is limited evidence for cardiovascular disease (CVD) risk associated with income dynamics over time among individuals with type 2 diabetes (T2D). Methods: Using a nationally representative sample from the Korean Health Insurance Service database, 1,528,108 adults with T2D aged 30-64 years and no history of CVD were enrolled between 2009-2012 (mean follow-up of 7.3 years). Using monthly health insurance premiums information, income levels were assessed annually for 4 years before the baseline year. Income variability was defined as the intraindividual standard deviation of the percent change in income across 5 years. The primary outcome was a composite event of incident fatal and nonfatal CVD (myocardial infarction, stroke, and heart failure) using insurance claims. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated after adjusting for potential confounders. Results: Sustained low income (i.e., lowest income quartile) over 5 years was associated with increased CVD risk (HRn=5years vs. n=0years 1.38, 95% CI 1.35-1.41; Ptrend<0.0001), whereas sustained high income (i.e., highest income quartile) was associated with decreased CVD risk (HR 0.71n=5years vs. n=0years 95% CI 0.70-0.72; Ptrend<0.0001). High-income variability was associated with increased CVD risk (HRhighest vs. lowest quartile 1.25, 95% CI 1.22-1.27; Ptrend<0.001). Individuals who experienced an income decline across 5 years leading up to baseline had increased CVD risk, particularly in a decrease to the lowest income level (i.e., Medical Aids beneficiaries), regardless of initial income status. Sensitivity analyses, including potential mediators, such as lifestyle-related factors and obesity, supported the results. Conclusions: Among non-elderly Korean adults with T2D, sustained low income, higher income variability, and income declines were associated with increased CVD risk. Our findings highlight the need to understand better the mechanisms by which income dynamics impact CVD risk among individuals with T2D.
The Mycobacterium tuberculosis genome at 25 years: lessons and lingering questions

First achieved in 1998 by Cole et al., the complete genome sequence of Mycobacterium tuberculosis continues to provide an invaluable resource to understand tuberculosis (TB), the leading cause of global infectious disease mortality. At the 25-year anniversary of this accomplishment, we describe how insights gleaned from the M. tuberculosis genome have led to vital tools for TB research, epidemiology, and clinical practice. The increasing accessibility of whole-genome sequencing across research and clinical settings has improved our ability to predict antibacterial susceptibility, to track epidemics at the level of individual outbreaks and wider historical trends, to query the efficacy of the bacille Calmette-Guérin (BCG) vaccine, and to uncover targets for novel antitubercular therapeutics. Likewise, we discuss several recent efforts to extract further discoveries from this powerful resource.
Cervical Adenosquamous Carcinoma: Detailed Analysis of Morphology, Immunohistochemical Profile, and Outcome in 59 Cases

Although both the 2014 and 2020 World Health Organization (WHO) criteria require unequivocal glandular and squamous differentiation for a diagnosis of cervical adenosquamous carcinoma (ASC), in practice, ASC diagnoses are often made in tumors that lack unequivocal squamous and/or glandular differentiation. Considering the ambiguous etiologic, morphologic, and clinical features and outcomes associated with ASCs, we sought to redefine these tumors. We reviewed slides from 59 initially diagnosed ASCs (including glassy cell carcinoma and related lesions) to confirm an ASC diagnosis only in the presence of unequivocal malignant glandular and squamous differentiation. Select cases underwent immunohistochemical profiling as well as human papillomavirus (HPV) testing by in situ hybridization. Of the 59 cases originally classified as ASCs, 34 retained their ASC diagnosis, 9 were reclassified as pure invasive stratified mucin-producing carcinomas, 10 as invasive stratified mucin-producing carcinomas with other components (such as HPV-associated mucinous, usual-type, or ASCs), and 4 as HPV-associated usual or mucinous adenocarcinomas with benign-appearing squamous metaplasia. Two glassy adenocarcinomas were reclassified as poorly differentiated HPV-associated carcinomas based on morphology and immunophenotype. There were no significant immunophenotypic differences between ASCs and pure invasive stratified mucin-producing carcinomas with regard to HPV and other markers including p16 expression. Although limited by a small sample size, survival outcomes seemed to be similar between all groups. ASCs should be diagnosed only in the presence of unequivocal malignant glandular and squamous differentiation. The 2 putative glassy cell carcinomas studied did not meet our criteria for ASC and categorizing them as such should be reconsidered.
Convergence-Zone PII : S 0893-6080 ( 97 ) 00016-6 Episodic Memory : Analysis and Simulations MARK MOLL 1 AND RISTOMIIKKULAINEN

Hunrun episodic memory provides a seemingly unlimited storage for everyday experiences, and a retrieval system that allows us to access the experiences with partial activation of their components. The system is believed to consist of afast, temporary storage in the hippocampus,and a slow, long-term storage within the neocortex. Thispaper presents a neural network model of the hippocampal episodic memory inspired by Darnusio’s idea of Convergence Zones. The model consists of a layer of perceptual feature maps and a binding layer. A perceptual feature pattern is coarse coded in the binding layer, and stored on the weights between layers. A partial activation of the stored features activates the bindingpattern, which in turn reactivates the entire storedpattem. For manyconfigurationsof the model, a theoretical lower boundfor the memory capacity can be derived, and it can bean order of magnitudeor higher than the number of all units in the model, and several orders of magnitude higher than the number of binding-layer units. Computational simulationsfirther indicate that the average capacity is an order of magnitude larger than the theoretical lower bound, and making the connectivity between layers sparser causes an even further increase in capacity. Simulationsalso show that ifntore descriptive bindingpatterns are used, the errors tend to be rnoreplausible (patterns are confused with other similar patters), with a slight cost in capacity. The convergence-zone episodic memory therefore accounts for the immediate storage and associative retrieval capability and large capacity of the hippocampal memory, and shows why the memory encoding areas can be much smaller than the perceptual maps, consist of rather coarse computational units, and are only sparsely connected to the perceptual maps. 01997 Elsevier Science Ltd. Keywords-Convergence zones,Episodicmemory, Associative memory, Long-termmemory, Content-addressable memory, Memorycapacity, Retrieval errors,Hippocarnpus.
Crocus sativus L. (Saffron) Stigma Aqueous Extract Induces Apoptosis in Alveolar Human Lung Cancer Cells through Caspase-Dependent Pathways Activation

Worldwide, lung cancer is the most common form of cancer. Saffron has been used in folk medicine for centuries. We investigated the potential of saffron to induce cytotoxic and apoptotic effects in lung cancer cells (A549). We also examined the caspase-dependent pathways activation of saffron-induced apoptosis against the A549 cells. A549 cells were incubated with different concentrations of saffron extract; then cell morphological changes, cell viability, and apoptosis were determined by the normal invertmicroscope, MTT assay, Annexin V and propidium iodide, and flow cytometric analysis, respectively. Activated caspases were detected by treatment of saffron in lung cancer cells using fluorescein-labeled inhibitors of polycaspases. The proliferation of the A549 cells were decreased after treatment with saffron in a dose- and time-dependent manner. The percentage of apoptotic cells increased with saffron concentrations. Saffron induced morphological changes, decreased percentage of viable cells, and induced apoptosis. Saffron could induce apoptosis in the A549 cells and activate caspase pathways. The levels of caspases involved in saffron-induced apoptosis in the A549 cells indicating caspase-dependent pathway were induced by saffron. The anticancer activity of the aqueous extract of saffron could be attributed partly to its inhibition of the cell proliferation and induction of apoptosis in cancer cells through caspase-dependent pathways activation.
Myocardial Ischemia / Reperfusion Injury in NADPH Oxidase – Deficient Mice

Previous studies have suggested that oxygen-derived free radicals are involved in the pathophysiology of myocardial ischemia/reperfusion (MI/R) injury. Specifically, neutrophils have been shown to mediate postischemic ventricular arrhythmias and myocardial necrosis. We hypothesized that MI/R injury would be reduced in the absence (2/2) of NADPH oxidase. Heterozygous control mice (n 523) and NADPH oxidase –/– mice (n524) were subjected to 30 minutes of coronary artery occlusion and 24 hours of reperfusion. Myocardial area at risk per left ventricle was similar in heterozygous control hearts (55 63%) and NADPH oxidase –/– hearts (6164%). Contrary to our hypothesis, the size of infarct area at risk was similar in the heterozygous control mice (42 64%) and NADPH oxidase –/– mice (3465%) (P5not significant). In addition, echocardiographic examination of both groups revealed that left ventricle fractional shortening was similar in NADPH oxidase –/– mice (n58; 2762.5%) and heterozygous control mice (n 510; 23.363.3%) after MI/R. Superoxide production, as detected by cytochrome c reduction, was significantly impaired ( P,0.01) in NADPH oxidase mice (n56) compared with heterozygous mice (n 57) (0.0460.03 versus 2.260.08 nmol O2·min ·10 cells). Intravital microscopy of the inflamed mesenteric microcirculation demonstrated that leukocyte rolling and adhesion were unaffected by the absence of NADPH oxidase. Oyster glycogen-stimulated neutrophil transmigration into the peritoneum was also similar in both the heterozygous control mice and NADPH oxidase –/– mice (P5not significant). These findings suggest that NADPH oxidase does not contribute to the development of myocardial injury and dysfunction after MI/R. (Circ Res. 2000;87:812–817.)