Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulation of CpG island promoters by the histone methyltransferase MLL2

MLL2 is a H3K4 specific HMT which vital for normal embryonic development in the mouse. Little is known on how MLL2 is recruited to its target genes and activates transcription. To gain insight into the molecular mechanism underlying MLL2 function, we focused on a known MLL2 target gene: Magoh2. This gene is controlled by a CpG island promoter and is ubiquitously expressed. Our results demonstrate that in the absence of MLL2, the Magoh2 promoter is methylated and Magoh2 is transcriptionally silenced. The Magoh2 promoter adopts the active conformation only in the presence of MLL2. Pol II is lost from the Magoh2 promoter in the absence of MLL2, resulting in Magoh2 down-regulation. We observed loss of H3K4me\(_3\)and H3K9ac and relocation of a nucleosome over the promoter, coinciding with the onset of DNA methylation. Use of ORB and a-amanitin demonstrated that neither transcription nor the presence of Pol II are required for the maintenance of H3K4me\(_3\). Magoh2 silencing can be overcome by re-introducing full-length MLL2. We investigated the role of MLL2 in haemopoiesis and demonstrated that MLL2 is vital for macrophage differentiation from embryoid bodies. MLL2 may be required for correct upregulation of Flk1 and generation of haem angioblast cells. When M//2 was deleted in haemangioblasts, the haemopoietic transcriptional program was perturbed suggesting that MLL2 may also play a role at this later developmental stage.
Panel‐based targeted exome sequencing reveals novel candidate susceptibility loci for age‐related cataracts in Chinese Cohort

Age‐related cataracts (ARC) is the most common blinding eye disease worldwide, and its incidence tend to become younger. However, the relationship between genetic factors and mechanisms is not fully understood. The aim of the study was to further clarify the relationship between ARC and genetic mechanisms in East Asian populations and to elucidate the pathogenesis.
Ortsgerichtete Rekombination in Chlamydomonas reinhardtii am Beispiel des Cre/lox-Systems

Die Grunalge Chlamydomonas reinhardtii hat sich in den vergangenen Jahrzehnten als Modellorganismus fur diverse zellbiologische Problemstellungen etabliert. Es wurde eine Vielzahl von Methoden entwickelt, welche die Transformation des Algengenoms erlauben. Wie auch in hoheren Pflanzen findet die Integration rekombinanter DNA nichthomolog, d.h. ungerichtet im Genom statt. Dies bedeutet, dass Positionseffekte, Mehrfachinsertionen und daraus resultierende Genstilllegungsmechanismen sowie mogliche Deletionen am Integrationsort die Genexpression des zu untersuchenden Transgens stark beeinflussen konnen und somit den direkten Vergleich unabhangiger Transformanten schwierig machen. Im Rahmen dieser Arbeit sollte eine Methode etabliert werden, welche die gezielte Veranderung des C. reinhardtii-Genoms mittels ortsgerichteter Rekombination zulasst. Das Cre/lox-Rekombinationssystem, welches aus der Cre-Rekombinase und der loxP-Erkennungssequenz besteht, wird bereits erfolgreich in E. coli, Hefe, Saugerzellen und einigen Pflanzen angewendet. Fur die ortsgerichtete Rekombination in Chlamydomonas wurde zuerst eine Expressionskassette mit einem Reportergen (ble-crluc) zwischen zwei identischen lox-Sequenzen unter der Kontrolle eines Tandem-Promotors und einem zweiten promotorlosen Selektionsmarkergen (aphVIII) in das Genom integriert. Mit Hilfe des entstandenen lox-Rezipienten-Stammes konnte durch die Cre-vermittelte Eliminierung des ble-crluc-Gens und der daraus resultierenden Aktivierung des aphVIII-Gens die Cre-Rekombinaseaktivitat im Kerngenom von C. reinhardtii untersucht werden. Es wurden verschiedene Strategien zur Bereitstellung der Cre-Rekombinase im Zellkern von C. reinhardtii untersucht. Sowohl die Einfuhrung eines gereinigten Cre-Enzyms mittels Elektroporation in die Zellen als auch die konstitutive Expression des cre-Gens in den Algen selbst fuhrte nicht zum gewunschten Erfolg. Da ein toxischer Effekt des Enzyms nicht ausgeschlossen werden konnte, wurde eine transiente Expression mit Hilfe der �Cre-Selbsteliminierungs�-Strategie realisiert. Dabei entfernt die Cre-Rekombinase ihre eigene kodierende Sequenz, welche sich ebenfalls zwischen zwei identischen lox-Erkennungssequenzen befindet, und limitiert somit selbst ihre Wirkungszeit auf das Algengenom. Diese Strategie ermoglichte erstmalig die ortsgerichtete Rekombination chromosomaler lox-Sequenzen in C. reinhardtii. Das Cre/lox-System bietet somit zukunftig einen effizienten Weg zur Entfernung von DNA-Sequenzen wie z.B. von Markergenen nach der erfolgreichen Transformation, aber auch eine Moglichkeit zur Integration rekombinanter DNA an spezifischen Stellen im Algengenom.
The association between the route of nutrition and serum levels of adipokines in critical illness: a pilot study

Background/aim Adipokines play an important role in the regulation of metabolism. In critical illness, they alter serum levels and are suspected to worsen clinical outcomes. But the effect of the route of nutrition on adipokines is not known. The purpose of this study was to evaluate the association between the route of nutrition and adipokine levels in critically ill patients. Materials and methods This prospective study was performed in an intensive care unit (ICU). Patients admitted to the ICU for least 72 h and receiving either enteral nutrition (EN) via tube feeding or parenteral nutrition (PN) were enrolled. Serum was obtained at baseline, 24 h, and 72 h for concentrations of leptin, adiponectin, resistin, glucagon–like peptide 1 (GLP–1), insulin–like growth factors 1 (IGF–1), and ghrelin. Results A total of 26 patients were included in the study. Thirteen patients received EN and 13 patients received PN. In the PN group, leptin level significantly increased (P = 0.037), adiponectin and ghrelin significantly decreased during follow up (P = 0.037, P = 0.008, respectively). There was no significant change between all adipokines in the EN group and resistin, IGF–1 and GLP–1 in the PN group during follow up. Resistin levels were markedly lower in the EN group at both 24 h (P = 0.015) and 72 h (P = 0.006) while GLP–1 levels were higher in the EN group at baseline, 24 h, and 72 h (P = 0.018, P = 0.005, and P = 0.003, respectively). There were no differences in leptin, adiponectin, IGF–1, and ghrelin levels over time. Conclusion The delivery of EN in critical illness was associated with decreased resistin levels and increased GLP–1 levels. Thus, the route of nutrition may impact the clinical outcome in critical illness due to adipokines.
Effects of Caffeine Ingestion on Physical Performance in Elite Women Handball Players: A Randomized, Controlled Study.

PURPOSE To investigate the effects of acute caffeine (CAFF) intake on physical performance in elite women handball players. METHODS A total of 15 elite women handball players participated in a randomized, double-blind study. In 2 different trials, participants ingested either a placebo (cellulose) or 3 mg of CAFF per kilogram of body mass (mg/kg bm) before undergoing a battery of neuromuscular tests consisting of handball throws, an isometric handgrip strength test, a countermovement jump, a 30-m sprint test (SV) and a modified version of the agility T test. Then, participants performed a simulated handball game (2 × 20 min), and movement patterns were recorded with a local positioning system. RESULTS Compared with the placebo, CAFF increased ball velocity in all ball throws (P = .021-.044; effect size [ES] = 0.39-0.49), strength in isometric handgrip strength test (350.8 [41.2] vs 361.6 [46.1] N, P = .034; ES = 0.35), and countermovement-jump height (28.5 [5.5] vs 29.8 [5.5] cm; P = .006; ES = 0.22). In addition, CAFF decreased running time in the SV (4.9 [0.2] vs 4.8 [0.3] s; P = .042; ES = -0.34). In the simulated game, CAFF increased the frequency of accelerations (18.1 [1.2] vs 18.8 [1.0] number/min; P = .044; ES = 0.54), decelerations (18.0 [1.2] vs 18.7 [1.0] number/min; P = .032; ES = 0.56), and body impacts (20 [8] vs 22 [10] impacts/min; P = .032; ES = 0.30). However, postexercise surveys about self-reported feelings of performance indicate that players did not feel increased performance with CAFF. CONCLUSION Preexercise ingestion of 3 mg/kg bm of CAFF improved ball-throwing velocity, jump, and sprint performance and the frequency of in-game accelerations and decelerations in elite women handball players.
Sex Differences in the Regulation of Vasopressin and Oxytocin Secretion in Bile Duct-Ligated Rats

Introduction: Hyponatremia due to elevated arginine vasopressin (AVP) secretion increases mortality in liver failure patients. No previous studies have addressed sex differences in hyponatremia in liver failure animal models. Objective: This study addressed this gap in our understanding of the potential sex differences in hyponatremia associated with increased AVP secretion. Methods: This study tested the role of sex in the development of hyponatremia using adult male, female, and ovariectomized (OVX) female bile duct-ligated (BDL) rats. Results: All BDL rats had significantly increased liver to body weight ratios compared to sham controls. Male BDL rats had hyponatremia with significant increases in plasma copeptin and FosB expression in supraoptic AVP neurons compared to male shams (all p < 0.05; 5–7). Female BDL rats did not become hyponatremic or demonstrate increased supraoptic AVP neuron activation and copeptin secretion compared to female shams. Plasma oxytocin was significantly higher in female BDL rats compared to female sham (p < 0.05; 6–10). This increase was not observed in male BDL rats. Ovariectomy significantly decreased plasma estradiol in sham rats compared to intact female sham (p < 0.05; 6–10). However, circulating estradiol was significantly elevated in OVX BDL rats compared to the OVX and female shams (p < 0.05; 6–10). Adrenal estradiol, testosterone, and dehydroepiandrosterone (DHEA) were measured to identify a possible source of circulating estradiol in OVX BDL rats. The OVX BDL rats had significantly increased adrenal estradiol along with significantly decreased adrenal testosterone and DHEA compared to OVX shams (all p < 0.05; 6–7). Plasma osmolality, hematocrit, copeptin, and AVP neuron activation were not significantly different between OVX BDL and OVX shams. Plasma oxytocin was significantly higher in OVX BDL rats compared to OVX sham. Conclusions: Our results show that unlike male BDL rats, female and OVX BDL rats did not develop hyponatremia, supraoptic AVP neuron activation, or increased copeptin secretion compared to female shams. Adrenal estradiol might have compensated for the lack of ovarian estrogens in OVX BDL rats.
Further Development of Near-Infrared Mediated Quantum Dots and Paclitaxel Co-loaded Nanostructured Lipid Carrier System for Cancer Theragnostic

Of colloidal systems, ceteris paribus, nanostructured lipid carriers are second to none in offering a single-unit platform for multifunctional benefits. Quantum dots are known to possess unique properties that make them ideal for imaging purpose and that they may be used for cancer detection. For several decades, paclitaxel has been the most effective drug against a wide range of solid tumours. Theragnostic nanomedicine provides a platform to monitor, evaluate, and individualize treatment in real time. Evaluation of cancer treatment outcome at an early stage therapy is key to increase survival prospects of a patient. Previously, a novel co-loaded nanostructured lipid carriers’ theragnostic system for parenteral administration was developed. The aim of this study was to further investigate the co-loaded nanostructured lipid carriers in order to provide interpretation necessary for preclinical elucidation of the formulation, in part. The co-loaded nanostructured lipid carriers were prepared by oil/water emulsification-solvent evaporation technique. In this study, stability and co-loaded nanostructured lipid carriers’ internalization by MCF 7 and HepG2 cells were investigated. The co-loaded nanostructured lipid carriers was stable at 4°C for 1 month. The formulation was successfully internalized by MCF-7 and HepG2 cells. Nevertheless, the co-loaded nanostructured lipid carrier was more apt for MCF-7 cells. This finding affirms the formulation to be the most appropriate for breast cancer treatment. In addition, if taken correctly by a patient for a month, the formulation would give true reflection of the contents’ amounts, the factor paramount to appropriate changes in treatment protocol. It can therefore safely be concluded that the co-loaded nanostructured lipid carrier formulation may be potentially an effective theragnostic translational system.
Total Atherosclerosis Burden of Baroreceptor-Resident Arteries Independently Predicts Blood Pressure Dipping in Patients With Ischemic Stroke

Supplemental Digital Content is available in the text. Nighttime blood pressure (BP) generally dips by 10% to 20% of the daytime values, and abnormal BP dipping may affect vascular health independently of BP level. The regulation of BP dipping involves arterial baroreflex, whose receptors mainly reside in carotid sinuses and aortic arch. Atherosclerosis in these baroreceptor-resident arteries (BRAs) is frequent among patients with ischemic stroke (IS) and might impair their BP-regulating capacity. We aimed to examine associations between atherosclerosis of BRA and BP dipping in patients with IS. BP dipping ratio was measured by 24-hour ambulatory blood pressure monitoring on the sixth day after IS. With computed tomography angiography, atherosclerosis conditions in 10 segments of carotid sinuses and aortic arch were scored and summed as total atherosclerosis burden of BRA. Among the 245 patients with IS, 78.0% had atherosclerosis in BRA. The total AS burden of BRA was negatively correlated with systolic BP dipping ratio (r=−0.331; P<0.001) and diastolic BP dipping ratio (r=−0.225; P<0.001). After adjusting for age, sex, vascular risk factors, 24-hour BP means, cervical and intracranial atherosclerosis scores, the negative correlations still existed (adjusted β, −0.259 [95% CI, −0.416 to −0.102] and adjusted β, −0.178 [95% CI, −0.346 to −0.010], respectively). In conclusion, higher total atherosclerosis burden of BRA was independently indicative of more blunted dipping of systolic BP and diastolic BP in IS. The total atherosclerosis burden of BRA might be important for predicting and managing BP dipping in patients with IS.
Trace Elements' Contamination of Pediatric Parenteral Nutrition Solutions in Canada: A Cause for Concern.

BACKGROUND Trace elements' (TEs) contamination of parenteral nutrition (PN) solutions is an ongoing concern. The aims of this study were 1) to measure actual TE concentrations in PN admixtures compared with ordered concentrations and 2) compare TE intake with current recommendations. METHODS PN admixtures from discarded bags were collected from patients receiving home PN and on inpatient wards. Samples were collected from 72 patients (39 inpatients, 33 receiving home PN). Age, percentage energy intake from PN, and PN orders were collected from patients' charts. PN samples were analyzed for TEs, including chromium (Cr) and manganese (Mn), and concentration measurements compared with ordered concentrations and current recommendations. RESULTS Measured Cr and Mn concentrations were higher than ordered concentrations: 5.3 ± 1.7 vs 2.8 ± 1.5 µg/L; P < 0.0001 and 11.9 ± 5.9 vs 0.00 µg/L; P < 0.0001, respectively. Chromium contamination alone accounted for over 100% of current recommendations for patients 0-12 months and between 63% and 92% for children >1 year. Contamination of Mn provided all the measured Mn in PN admixtures, since Mn is excluded from PN orders at our institution. Between 70% and 120% of current Mn recommendations were met from contamination. CONCLUSIONS Cr should be excluded from PN admixtures for children 0-12 months and only one-fourth the current recommendation should be added for pediatric patients >1 year. Manganese should also be excluded from PN admixture for pediatric patients but plasms monitoring 2-3 times per year is recommended for those on long-term PN.
Adherence to Cervical Cancer Screening in Korean American Immigrant Women: Identifying Malleable Variables for Intervention Development

Introduction. Despite Korean American women having a high incidence rate of cervical cancer, many are unaware of the significance of Pap test. The purpose of this research was to examine the rates of Pap test receipt and factors associated with the uptake. Method. The study was guided by Andersen’s Model of Health Service Use and used a cross-sectional research design. A sample of 230 women residing in metro-Atlanta, Georgia, participated in this study. Results. Slightly more than half (55.7%) had lifetime Pap tests while less than half (45.7%) had it within the last 3 years. Binary logistic regression indicated that marital status, monthly income, and annual checkups were significantly correlated with receiving Pap tests. Discussion. Special attention is needed for women who are unmarried and have low income to increase Pap test receipt. Suggested intervention programs include better communication strategies, extended Medicare coverage, and outreach programs within Korean American community.
An ancestral regulatory mechanism underlies Hoxd gene expression in both developing genitals and digits

Keywords: Hox ; gene ; regulation ; transcription ; genital tubercle ; external genitalia ; digits ; epigenetic ; chromatin ; enhancers ; topological domains ; regulatory landscape ; long-range control ; genomic imprinting ; Dlx genes ; Itga6 ; DNA methylation ; chromatin architecture These Ecole polytechnique federale de Lausanne EPFL, n° 5997 (2013)Programme doctoral Approches moleculaires du vivantFaculte des sciences de la vieInstitut suisse de Recherche Experimentale sur le Cancer Unite du Prof. Duboule Jury: Prof. B. Lemaitre, president du jury, Prof. D. Duboule, directeur de these, Prof. B. Deplancke, rapporteur, Prof. A. Reymond, rapporteur, Dr F. Spitz, rapporteur Public defense: 2013-12-20 Reference doi:10.5075/epfl-thesis-5997Print copy in library catalog Record created on 2013-12-09, modified on 2017-05-12
COPD Positive Screening with Spirometry Increases Motivation to Quit Tobacco Smoking in an Addiction Treatment Center

Abstract Providing an on-site immediate diagnosis of Chronic Obstructive Pulmonary Disease (COPD) and lung age in tobacco smokers could be a motivational tool for smoking cessation. Our aim was to investigate the effects of an abnormal spirometry results on motivational change and subsequent smoking cessation. We conducted a retrospective analysis of smoking status after 3 months of tobacco counseling. Patients were recruited in an addiction outpatient center. Spirometry results were obtained with a portable device during the first visit. The sample was thus divided in 3 groups: COPD, subthreshold-group (no COPD but abnormal lung age) and normal spirometry. Among the three groups, we compared the immediate motivation change, difference in Q-MAT motivation scale score after minus before spirometry (Kruskal-Wallis test) and the smoking status after 3 months (Fisher test). We included 48 patients (37 males, median age 44 years, median cigarette-per-day 20). Spirometry results divided the sample in COPD (N = 13), subthreshold (N = 11) and normal group (N = 24). Mean Q-MAT score change after spirometry was different between groups (p = 0.019), greater in COPD (4.62 ± 3.38) than normal group (1.46 ± 3.11), and lower in patient with a co-occuring hazardous alcohol use (p = 7.6 × 10−3). Three-months smoking status was different between spirometry results groups (p = 0.0021). COPD (5/13, 38.5%) and subthreshold patients (6/10, 60.0%) had stopped more frequently than patients from the normal-group (2/22, 9.1%). The effect of immediate spirometry results on motivation to quit varies according to the screened pulmonary damages and hazardous alcohol use. It could be a useful tool in addiction treatment centers.
Processing induced changes in physicochemical structure properties and nutrient metabolism and their association in cool-season faba (CSF: Vicia L.), revealed by vibrational FTIR spectroscopy with chemometrics and nutrition modeling techniques

Abstract This review aims to update recent progress in processing induced molecular structure changes in the association of physicochemical structure properties with nutritional metabolism in cool-season faba bean (Vicia L.), which was revealed using advanced vibrational molecular spectroscopy in combination with chemometrics and advanced nutrient modeling techniques. The review focused on strategies to improve the utilization of the cool-season faba bean through heat-related technological treatments and the relationship of the processing induced molecular structural changes to nutrient delivery and metabolism in ruminant systems. The updated methods with truly absorption nutrient modeling techniques and advanced vibrational molecular spectroscopy techniques sourced by globar and synchrotron radiation (e.g. NIR, near Infrared, FTIR, Fourier transform infrared, DRIFT, diffuse reflectance infrared Fourier transform, ATR-FTIR, attenuated total reflectance-FTIR, FTIRM, FTIR micro-spectroscopy, SR-FTIRM, synchrotron radiation- FTIRM) to study cool-season faba bean were reviewed. This article provides an insight and a new approach on how to combine advanced nutrient modeling techniques with cutting-edge vibrational molecular spectroscopic techniques to study the processing induced molecular structure change in relation to molecular nutrition of cool-season Vicia faba as well as the interaction between molecular structure and molecular nutrition.