Miracle-dz/UniFAR-FTUs huggingface dataset:
IL-22 Fate Reporter Reveals Origin and Control of IL-22 Production in Homeostasis and Infection

IL-22 is a cytokine that regulates tissue homeostasis at barrier surfaces. A variety of IL-22–producing cell types is known, but identification on the single-cell level remains difficult. Therefore, we generated a fate reporter mouse that would allow the identification of IL-22–producing cells and their fate mapping in vivo. To trace IL-22–expressing cells, a sequence encoding Cre recombinase was cloned into the Il22 locus, and IL22Cre mice were crossed with reporter mice expressing enhanced yellow fluorescence protein (eYFP) under control of the endogenous Rosa26 promoter. In IL22CreR26ReYFP mice, the fluorescent reporter permanently labels cells that have switched on Il22 expression, irrespective of cytokine production. Despite a degree of underreporting, eYFP expression was detectable in nonimmune mice and restricted to group 3 innate lymphoid cells (ILC3) in the gut and γδ T cells in skin or lung. Upon skin challenge with imiquimod, eYFP+ γδ and CD4 T cells expanded in the skin. Infection with Citrobacter rodentium initially was controlled by ILC3, followed by expansion of eYFP+ CD4 T cells, which were induced in innate lymphoid follicles in the colon. No eYFP expression was detected in small intestinal Th17 cells, and they did not expand in the immune response. Colonic eYFP+ CD4 T cells exhibited plasticity during infection with expression of additional cytokines, in contrast to ILC3, which remained largely stable. Single-cell quantitative PCR analysis of eYFP+ CD4 T cells confirmed their heterogeneity, suggesting that IL-22 expression is not confined to particular subsets or a dedicated Th22 subset.
What's in a smile? Neural correlates of facial embodiment during social interaction

Abstract Previous investigations have shown that the perception of socially relevant facial expressions, indicating someone else's intention to communicate (e.g., smiling), correlate with increased activity in zygomaticus major muscle regardless of whether the facial expressions seen are directed towards the human observer or toward someone else (Mojzisch et al., 2006). These spontaneous, involuntary reactions have been described as facial mimicry and seem to be of considerable importance for successful interpersonal communication. We investigated whether specific neural substrates underlie these responses by performing a finite impulse response (FIR) analysis of an experiment using functional magnetic resonance imaging (fMRI) to investigate the perception of socially relevant facial expressions (Schilbach et al., 2006). This analysis demonstrates that differential neural activity can be detected relative to the FIR time window in which facial mimicry occurs. The neural network found includes but extends beyond classical motor regions (face motor area) recruiting brain regions known to be involved in social cognition. This network is proposed to subserve the integration of emotional and action-related processes as part of a pre-reflective, embodied reaction to the perception of socially relevant facial expressions as well as a reflective representation of self and other.
The Female Post-Mating Response Requires Genes Expressed in the Secondary Cells of the Male Accessory Gland in Drosophila melanogaster

Seminal proteins from the Drosophila male accessory gland induce post-mating responses (PMR) in females. The PMR comprise behavioral and physiological changes that include increased egg laying, decreased receptivity to courting males, and changes in the storage and use of sperm. Many of these changes are induced by a “sex peptide” (SP) and are maintained by SP’s binding to, and slow release from, sperm. The accessory gland contains two secretory cell types with distinct morphological and developmental characteristics. Products of these “main” and “secondary” cells work interdependently to induce and maintain the PMR. To identify individual genes needed for the morphology and function of secondary cells, we studied iab-6cocu males, whose secondary cells have abnormal morphology and fail to provide products to maintain the PMR. By RNA-seq, we identified 77 genes that are downregulated by a factor of >5× in iab-6cocu males. By functional assays and microscopy, we tested 20 candidate genes and found that at least 9 are required for normal storage and release of SP in mated females. Knockdown of each of these 9 genes consequently leads to a reduction in egg laying and an increase in receptivity over time, confirming a role for the secondary cells in maintaining the long-term PMR. Interestingly, only 1 of the 9 genes, CG3349, encodes a previously reported seminal fluid protein (Sfp), suggesting that secondary cells may perform essential functions beyond the production and modification of known Sfps. At least 3 of the 9 genes also regulate the size and/or abundance of secondary cell vacuoles, suggesting that the vacuoles’ contents may be important for the machinery used to maintain the PMR.
Ionic control of chromosome architecture in living and permeabilized cells.

Studies with isolated chromatin show that higher order chromosome architecture can be regulated by ionic conditions; however, the physiological relevance of these findings remains unknown. In the present study, chromosome architecture was analyzed in situ in living and detergent-extracted cells exposed to different ionic conditions. In intact mitotic endothelial cells, chromosomes instantly unfolded as detected by phase contrast microscopy when the salt concentration in the culture medium was increased from 110 to 410 mM NaCl or from 0 to 65 mM MgCl2. When the ions were removed and the preexisting culture conditions were restored, chromosomes refolded into their original shapes and subsequently underwent mitotic division. Similar reversible effects were observed on nucleolar structure in living interphase cells as well as on mitotic chromosomes exposed to high salt after cell membranes were removed by treatment with Triton X-100. This permeabilized mitotic cell model was then used to identify proteins that remained tightly associated with chromatin during the ion-driven chromosome unfolding-refolding cycle and which therefore could be important for maintenance of chromosome structure. Under these conditions in which disassembled chromosomes retained their ability to fully recondense, more than 95% of Topoisomerase I was extracted whereas approximately 25% of Topoisomerase IIalpha and 50% of Histone H1 remained tightly associated with chromatin. These data demonstrate the sensitivity of chromosome structure to variations in ionic concentration in situ and suggest that there are at least two distinct pools of Histone H1 and Topoisomerase IIalpha associated with chromatin during mitosis, one of which may be required for chromosome compaction.
Inhibitory effect of melatonin on cataract formation in newborn rats: Evidence for an antioxidative role for melatonin

Abe M, Reiter RJ, Orhii PB, Hara M, Poeggeler B. Inhibitory effect of melatonin on cataract formation in newborn rats: Evidence for an antioxidative role for melatonin. J. Pineal Res. 1994; 17: 94–100. ©Munksgaard 1994
Ethnicity and physician-older patient communication about alternative therapies.

OBJECTIVES The purpose of this study was to describe ethnic differences in physician-patient communication about alternative therapies, using a data set comprised of audiotapes and transcripts of primary care medical visits. METHODS The data set was collected during 1995 at the family practice and general medicine clinics at the University of New Mexico Health Sciences Center, Albuquerque, NM. Twenty-seven (27) resident physicians and 205 of their Hispanic and non-Hispanic white patients age 50 and over participated. RESULTS Almost 18 percent of patients reported using one or more alternative therapies during the preceding month. Herbal medicine was the most widely used therapy. Eighty-three percent (83%) of patients who reported using an alternative therapy in the previous month did not tell their physicians. Physicians asked one or more questions about alternative therapies during only 3.4% of encounters. Only 2% of patients asked their physicians one or more questions about alternative therapies. There were no ethnic differences in physician-older patient communication about alternative therapies. DISCUSSION Physician-patient communication could be improved to enhance physician understanding of the spectrum of interventions patients pursue to improve their health.
Demands on Caring Relatives of Head and Neck Cancer Patients

Background: Relatives of cancer patients experience high levels of stress that influence the quality of life of these individuals. To investigate whether there is a necessity for simultaneous supportive care of patient relatives, we performed for the first time a study asking the closest relatives of head and neck cancer patients about their needs during and after the treatment to consider how to optimize the situation for such patient groups.
Pharmacodynamic effects of a new fixed-dose clopidogrel–aspirin combination compared with separate administration of clopidogrel and aspirin in patients treated with coronary stents: The ACCEL-COMBO trial

Abstract Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin is a widely prescribed regimen to prevent ischemic events in patients undergoing percutaneous coronary intervention (PCI). A fixed-dose combination (FDC) capsule (HCP0911) has been developed to provide dosing convenience and improve adherence. We compared the antiplatelet effects of single daily dose HCP0911 with separate treatment with daily 75 mg clopidogrel plus 100 mg aspirin. This was a randomized, open-label, two-period, crossover, non-inferiority study conducted in stented patients who had been treated for at least 6 months with clopidogrel and aspirin. Thirty patients were randomly assigned to receive either daily 75 mg clopidogrel plus 100 mg aspirin treatment or HCP0911 for 2 weeks and then were crossed over to the other treatment for 2 weeks. Pharmacodynamic effects were measured with VerifyNow, light transmittance aggregometry (LTA), and thromboelastography (TEG®). The primary endpoint was P2Y12 Reaction Units (PRU) measured by VerifyNow. PRUs during treatment with HCP0911 were not inferior to those during separate treatment (202 ± 52 vs. 207 ± 60 PRU; mean difference, −5 PRU; 90% confidence interval of difference, −23 to 13 PRU; P for non-inferiority = 0.015 for predetermined limit). “BASE” and Aspirin Reaction Units by VerifyNow did not differ between the two treatments. During each treatment, there were no differences in maximal and final platelet aggregations by LTA (all P values ≥0.822) and TEG® measurements. In conclusion, in stented patients, the antiplatelet effect of a fixed-dose clopidogrel–aspirin combination, HCP0911, was not inferior to separate administration of clopidogrel and aspirin.
ELABORATION ON IMMIGRATION AND RISK FOR SCHIZOPHRENIA

Background Being a small and culturally different minority, or having a different appearance, has been invoked to account for the increased prevalence of psychotic disorders among immigrants. The majority of the Jewish Israeli population are first- or second-generation immigrants from Europe, North Africa or Asia, and during the late 1980s and 1990s, 885 000 persons immigrated to Israel from the former Soviet Union and 43 000 immigrated from Ethiopia. These Ethiopian immigrants came from a very different culture compared to the rest of the population, and have a distinct appearance. To further understand the association between immigration and schizophrenia, we compared risk for later schizophrenia between adolescents who immigrated from Ethiopia with risk among the other immigrant groups, and with native-born Israelis. Method Of 661 792 adolescents consecutively screened by the Israeli Draft Board, 557 154 were native-born Israelis and 104 638 were immigrants. Hospitalization for schizophrenia was ascertained using a National Psychiatric Hospitalization Case Registry. All analyses controlled for socio-economic status (SES). Results Risk for schizophrenia was increased among both first- [hazard ratio (HR) 1.62, 95% confidence interval (CI) 1.18–2.22] and second-generation immigrants [HR 1.41, 95% CI 1.01–1.95 (one immigrant parent) and HR 1.49, 95% CI 1.11–2.0 (two immigrant parents)]. When risk for schizophrenia was calculated for each immigrant group separately, immigrants from Ethiopia were at highest risk of later schizophrenia (HR 2.95, 95% CI 1.88–4.65). Conclusion This comparison between diverse groups of immigrants supports the notion that immigrants who differ in culture and appearance from the host population are at increased risk for schizophrenia.
Bleeding events with dabigatran or warfarin in patients with venous thromboembolism

Summary Dabigatran was as effective as warfarin for the acute treatment of venous thromboembolism in the RE-COVER and RE-COVER II trials. We compared the incidence of bleeding with dabigatran versus warfarin in pooled data from these studies. The localisation, bleeding severity, and the impact of key factors on the incidence of bleeding, were compared between the dabigatran and warfarin treatment group. Altogether, 2553 patients received dabigatran and 2554 warfarin, each for a mean of 164 days. The incidence of any bleeding event was significantly lower with dabigatran (hazard ratio [HR] 0.70; 95 % confidence interval [CI], 0.61–0.79), as was the incidence of the composite of MBEs and clinically relevant non-major bleeding events (HR 0.62; 95 % CI, 0.50–0.76). The incidence of major bleeding events (MBEs) was also significantly lower with dabigatran in the double-dummy phase (HR, 0.60; 95 % CI, 0.36–0.99) but not statistically different between the two treatment arms when the entire treatment period is considered (HR 0.73 95 % CI, 0.48–1.11). Increasing age, reduced renal function, Asian ethnicity, and concomitant antiplatelet therapy were associated with higher bleeding rates in both treatment groups. The reduction in bleeding with dabigatran compared to warfarin was consistent among the subgroups and with a similar pattern for intracranial, and urogenital major bleeding. In conclusion, treatment of venous thromboembolism with dabigatran is associated with a lower risk of bleeding compared to warfarin. This reduction did not differ with respect to the location of bleeding or among predefined subgroups.
Homografts in aortic position: does blood group incompatibility have an impact on patient outcomes?

OBJECTIVES Aortic homografts are an alternative to mechanical or biological valve prostheses. Homografts are generally not transplanted ABO-compatible while this policy is still under debate. The purpose of this study was to investigate whether ABO compatibility impacts on long-term outcomes or not. METHODS Between 1992 and 2009, 363 adult patients with a mean age of 52 years received homografts in aortic position. Donor and acceptor blood groups could be obtained for 335 patients. Sixty-three percent received blood group-compatible (n = 212) (Group iso) and 37% non-blood group-compatible allografts (n = 123) (Group non-iso). RESULTS The overall event-free survival (freedom from death or reoperation) was 55.5% (n = 186). In the iso group, the event-free survival was 84.1% at 5 years and 63.3% at 10 years. In the non-iso group, the event-free survival was 79.4% at 5 years and 51.8% at 10 years. 28.5% of patients (n = 35) with ABO-incompatible and 25.5% (n = 54) with ABO-compatible grafts required reoperation. The mean time to reoperation in the iso group was 97.3 vs 90 months in the non-iso group. CONCLUSIONS In 17 years of research, we have not yet found a statistical significant difference in blood group incompatibility regarding overall event-free survival. In our opinion, there is no need to use ABO-compatible homografts for aortic valve replacement in adults. Histological and immunohistochemical assays are mandatory to confirm our results.
The Delayed Quinacrine Mustard Fluorescence from the C-blocks of Apodemus argenteus Is Due to the Introduction of Nicks into the DNA

Abstract “Delayed QM-fluorescence” refers to the unusual kinetics of fluorescence from most of the C-heterochromatic regions of the chromosomes of the small Japanese field mouse Apodemus argenteus. When stained with quinacrine mustard (QM-stained), these C-heterochromatic regions emit weak fluorescence immediately after exposure to blue light (BL); they emit bright fluorescence within a few minutes; and the intensity of the fluorescence gradually decreases after maximum fluorescence has been recorded. To elucidate the mechanism of this phenomenon, we used acridine orange staining (AO-staining) and a modified version of the in situ nick-translation method. Focusing on the large C-heterochromatic region (C-block) of the X chromosome, we noted that AO-stained C-blocks emitted greenish fluorescence, while QM-stained and BL-exposed (QM-BL-processed) C-blocks emitted reddish fluorescence upon AO-staining after removal of QM. These findings suggested that the C-block DNA of A. argenteus might undergo a structural change, such as strand breaks, during QM-BL processing. Application of the modified in situ nick-translation method revealed the generation of an appreciable number of nicks in the C-block DNA by QM-BL processing. No such nick formation was observed in the C-blocks of three other mammalian species: Apodemus peninsulae, Microtus montebelli, and Urotrichus talpoides. Our findings support the hypothesis that nick formation due to exposure to BL might play a primary role in inducing delayed QM-fluorescence in the C-blocks of A. argenteus. On the basis of the present and earlier findings, we propose a probable mechanism for delayed QM-fluorescence in A. argenteus chromosomes.
Endoscopic balloon dilatation of benign gastric outlet obstruction

Background and Aim: Endoscopic balloon dilatation (EBD) has been used for the treatment of gastric outlet obstruction (GOO). There are several reports on the utility and success of this non‐surgical treatment option in peptic GOO, with variable results. However, there are only a few reports documenting the efficacy of this method for non‐peptic GOO. The authors here report on experience with balloon dilatation in peptic and non‐peptic GOO over a 3‐year period.
Cigarette smoke extract potentiates bradykinin-induced increases in microvascular permeability.

The first goal of this study was to determine whether cigarette smoke extract (CSE) increases microvascular permeability of the hamster cheek pouch in vivo. The second goal was to determine whether CSE potentiates bradykinin-induced increases in vascular permeability in the hamster cheek pouch. Using intravital microscopy, we examined the permeability of the hamster cheek pouch to fluorescein isothiocyanate-dextran (mol wt 70,000). Increases in permeability were quantitated by counting the number of postcapillary venular leaky sites per 0.11 cm2. Superfusion of CSE (1, 5, and 10%) did not produce venular leaky sites and, thus, did not alter macromolecular permeability. Superfusion of bradykinin (0.1, 0.5, and 1.0 microM) produced a dose-related increase in the number of venular leaky sites. Formation of leaky sites in response to bradykinin was potentiated by CSE. To determine whether potentiation of bradykinin-induced leaky site formation by CSE was related to products released via the cyclooxygenase pathway, we examined the effects of pretreatment with indomethacin (10 mg/kg i.v.). Indomethacin did not alter the potentiating effect of CSE on bradykinin-induced leaky site formation. These findings suggest that CSE does not alter basal permeability of the hamster cheek pouch microcirculation in vivo. However, CSE potentiates bradykinin-induced increases in microvascular permeability. The mechanism of CSE-induced potentiation of microvascular permeability does not appear to be related to substances produced via the cyclooxygenase pathway.
Distribution of Inflammation Within Carotid Atherosclerotic Plaques With High-Risk Morphological Features: A Comparison Between Positron Emission Tomography Activity, Plaque Morphology, and Histopathology

Background— Several high-risk morphological features (HRM) of plaques, especially in combination, are associated with an increased risk of a clinical event. Although plaque inflammation is also associated with atherothrombosis, the relationship between inflammation and number of HRM is not well understood. Methods and Results— Thirty-four patients underwent 18flurodeoxyglucose positron emission tomography (FDG-PET) imaging, and carotid atherosclerotic inflammation was assessed (target-to-background ratio). Additionally, in a subset of 10 subjects with carotid stenosis who underwent carotid endarterectomy, inflammation was histologically assessed (CD68 staining). Vessel wall morphology was examined using computed tomography for the presence of visible plaque and presence of 3 HRM: positive remodeling, luminal irregularity, and low attenuation. A total of 100 vascular segments were analyzed, of which 69 contained visible plaque (26 plaques with ≥1 HRM). Inflammation, by FDG uptake (target-to-background ratio), was higher in plaques with (versus without) HRM (mean±SEM: 2.21±0.20 versus 1.66±0.07, P=0.0003) and increased with the number of HRM observed (P<0.001 for trend). Similarly, inflammation within atherosclerotic specimens (% CD68 staining) was higher in plaques with (versus without) HRM (median [interquartile range]: 10 [0, 19.85] versus 0 [0, 1.55], P=0.01) and increased with the number of HRM observed (P<0.001 for trend). Conclusions— Inflammation, as assessed by both FDG uptake and histology, is increased in plaques containing HRM and increases with increasing number of HRM. These data support the concept that inflammation accumulates relative to the burden of morphological abnormalities.
PI3K/mTORC1 activation in hamartoma syndromes: Therapeutic prospects

Dysregulated activity of phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin complex 1 (mTORC1) is characteristic feature of hamartoma syndromes. Hamartoma syndromes, dominantly inherited cancer predisposition disorders, affect multiple organs and are manifested by benign tumors consisting of various cell types native to the tissues in which they arise. In the past few years, three inherited hamartoma syndromes, Cowden syndrome (CS), tuberous sclerosis complex (TSC) syndrome, and Peutz-Jeghens syndrome (PJS), have all been linked to a common biochemical pathway: the hyperactivation of PI3K/mTORC1 intracellular signaling. Three tumor suppressors, PTEN (phosphatases and tensin homolog), tuberous sclerosis complex TSC1/TSC2, and LKB1, are negative regulators of PI3K/mTORC1 signaling; disease-related inactivation of these tumor suppressors results in the development of PTEN-associated hamartoma syndromes, TSC, and PJS, respectively. The goal of this review is to provide a roadmap for navigating the inherently complex regulation of PI3K/mTORC1 signaling while highlighting the progress that has been made in elucidating the cellular and molecular mechanisms of hamartoma syndromes and identificating potential therapeutic targets for their treatment. Importantly, because the PI3K/mTORC1 pathway is activated in the majority of common human cancers, the identification of novel molecular target(s) for the treatment of hamartoma syndromes may have a broader translational potential, and is critically important not only for therapeutic intervention in hamartoma disorders, but also for the treatment of cancers.