Miracle-dz/UniFAR-FTUs huggingface dataset:
Canonical nucleosome organization at promoters forms during genome activation

The organization of nucleosomes influences transcriptional activity by controlling accessibility of DNA binding proteins to the genome. Genome-wide nucleosome binding profiles have identified a canonical nucleosome organization at gene promoters, where arrays of well-positioned nucleosomes emanate from nucleosome-depleted regions. The mechanisms of formation and the function of canonical promoter nucleosome organization remain unclear. Here we analyze the genome-wide location of nucleosomes during zebrafish embryogenesis and show that well-positioned nucleosome arrays appear on thousands of promoters during the activation of the zygotic genome. The formation of canonical promoter nucleosome organization is independent of DNA sequence preference, transcriptional elongation, and robust RNA polymerase II (Pol II) binding. Instead, canonical promoter nucleosome organization correlates with the presence of histone H3 lysine 4 trimethylation (H3K4me3) and affects future transcriptional activation. These findings reveal that genome activation is central to the organization of nucleosome arrays during early embryogenesis.
AASLD public policy statement should be evidence‐based

We appreciate Dr. Fujita’s valuable input regarding an animal model of chronic endotoxemia and the role of regulatory T cells (Tregs) in liver disease. Cani and colleagues recently reported that a high-fat diet increases plasma lipopolysaccharide (LPS) level.1 Chronic infusion of LPS in mice fed a normal diet causes a metabolic response similar to high-fat feeding, including obesity, insulin resistance, and increased liver triglyceride content. In this sense, the high-fat diet mouse model that we use represents a model of chronic endotoxemia. Our acute exogenous LPS experiments merely reflect an exacerbated inflammatory status that helped us to determine the role of Tregs in modulation of hepatic inflammation under a fatty liver condition.2 Tregs express several members of Toll-like receptors (TLR). Exposing Tregs to LPS induces up-regulation of several activation markers and enhances Treg survival and proliferation.3 In addition, LPS treatment increases Treg suppression efficiency in vitro and in vivo. Therefore, it will be interesting to compare the number and the function of hepatic Tregs in the model of chronic exogenous LPS infusion to the model of high-fat diet–induced fatty liver disease.
Prevention and control of bovine respiratory disease.

Bovine respiratory disease (BRD) constitutes one of the key health issues and most costly problems occurring in cattle in the U.S and all part of the world. Increased morbidity and mortality, decreased weight gains, decreased feed utilization, decrease carcass quality and increased prophylaxis and therapy lead to enormous economic losses. This is a disease complex that involves multiple microbial pathogens (viruses and bacteria), environmental and host predisposing risk factors. Increasing beef and dairy production in all part of the world will benefit from improved prevention and control of BRD. The use of management strategies, such as preconditioning programs, has a significant potential to decrease BRD cases and overall negative impact. Other programs, such as metaphylaxis, are useful in situations where calves entering a feedlot are at “high risk” for developing BRD. The cattle health industry should continue to identify means of BRD control though the development and use of new technologies with the aim of enhancing resistance, reducing risk factors and decreasing pathogen exposure.
Study on Routing Protocols Classification in Sensor Network

A Sensor Network is one of congested network defined under the sensing range and energy limitations. To provide energy effective communication, there are different network architectures to control the network communication. These architectures are defined under the rules of relative protocols. In this paper, studies on different associated classes to the routing protocols in sensor network are defined. Paper explored these protocols along with their utility and application area.
EPIZOOTIOLOGY OF SKUNK RABIES IN NORTH AMERICA

Public health surveillance data from the United States and Canada (1961 to 1982) were analyzed to determine if consistent temporal and spatial patterns in skunk rabies could be identified. Enzootic/epizootic rabies was recognized in 18 states (enzootic states) based on the criteria of ≥20 yr of reported skunk rabies and at least 1 yr with a minimum of 50 reported rabid skunks. In other wildlife species, epizootics have been demonstrated to expand along a wave-like front. We hypothesized: if skunk rabies behaved in a similar fashion, states reporting rabid skunks would change over time. No such change was noted. During epizootics the number of counties reporting increased but not the number of states. Within Illinois certain counties were demonstrated to have persistent rabies histories and likely served as enzootic foci. Enzootic states combined prevalence indicated a 6 to 8 yr cycle for epizootics. Data on monthly percent rabies positive (number rabid/total number tested) were available from six states and Canada. Mean distributions were bimodal with winter and spring peaks. The patterns identified for skunk rabies differ from those of other major wildlife vectors and have significance for potential vaccination control regimes.
[Investigation of p53 gene mutations in keloids using PCR-SSCP].

OBJECTIVE To detect gene mutations of p53 gene (exon 4-6) in fibroblasts. METHODS Samples of keloids were taken from 15 patients. The mutations of p53 gene were detected using polymerase chain reaction, the single-strand conformational polymorphism(SSCP) analysis and DNA sequencing. RESULTS Gene mutations in p53 gene exon 4, 5, and 6 were identified in all the patients with keloids. CONCLUSION Gene mutations resulted in keloid p53 protein losing its functions of suppressing cell processes and conducting apoptosis.
Lopinavir/Ritonavir Induces the Hepatic Activity of Cytochrome P450 Enzymes CYP2C9, CYP2C19, and CYP1A2 But Inhibits the Hepatic and Intestinal Activity of CYP3A as Measured by a Phenotyping Drug Cocktail in Healthy Volunteers

Objective: The effect of lopinavir/ritonavir (LPV/r) administration on cytochrome P450 (CYP) enzyme activity was quantified using a phenotyping biomarker cocktail. Changes in CYP2C9, CYP2C19, CYP3A, CYP1A2, N-acetyltransferase-2 (NAT-2), and xanthine oxidase (XO) activities were evaluated using warfarin (WARF) + vitamin K, omeprazole (OMP), intravenous (IV) and oral (PO) midazolam (MDZ), and caffeine (CAF). Design: Open-label, multiple-dose, pharmacokinetic study in healthy volunteers. Methods: Subjects (n = 14) simultaneously received PO WARF 10 mg, vitamin K 10 mg, OMP 40 mg, CAF 2 mg/kg, and IV MDZ 0.025 mg/kg on days (D) 1 and 14, and PO MDZ 5 mg on D2 and D15. LPV/r (400/100 mg twice daily) was administered on D4-17. CYP2C9 and CYP2C19 activities were quantified by S-WARF AUC0-inf and OMP/5-hydroxy OMP ratio, respectively. CYP1A2, NAT-2, and XO activities were quantified by urinary CAF metabolite ratios. Hepatic and intestinal + hepatic CYP3A activities were quantified by IV (CL) and PO (CL/F) MDZ clearance, respectively. Results: After LPV/r therapy, CYP2C9, CYP2C19, and CYP1A2 activity increased by 29%, 100%, and 43% (P = 0.001, 0.046, and 0.001), respectively. No changes were seen in NAT-2 or XO activity. Hepatic and intestinal + hepatic CYP3A activity decreased by 77% (P < 0.001) and 92% (P = 0.001), respectively. Conclusion: LPV/r therapy results in modest induction of CYP1A2 and CYP2C9 and potent induction of CYP2C19 activity. Increasing doses of concomitant medications metabolized by these enzymes may be necessary. LPV/r inhibited intestinal CYP3A to a greater extent than hepatic CYP3A activity. Doses of concomitant CYP3A substrates should be reduced when combined with LPV/r, although intravenously administered compounds may require less of a relative dose reduction than orally administered compounds.
Estrogen and the vascular system Effects of estrogen on the vascular system

The cardiovascular protective actions of estrogen are partially mediated by a direct effect on the vessel wall. Estrogen is active both on vascular smooth muscle and endothelial cells where functionally competent estrogen receptors have been identified. Estrogen administration promotes vasodilation in humans and in experimental animals, in part by stimulating prostacyclin and nitric oxide synthesis, as well as by decreasing the production of vasoconstrictor agents such as cyclooxygenase-derived products, reactive oxygen species, angiotensin II, and endothelin-1. In vitro, estrogen exerts a direct inhibitory effect on smooth muscle by activating potassium efflux and by inhibiting calcium influx. In addition, estrogen inhibits vascular smooth muscle cell proliferation. In vivo, 17ß-estradiol prevents neointimal thickening after balloon injury and also ameliorates the lesions occurring in atherosclerotic conditions. As is the case for other steroids, the effect of estrogen on the vessel wall has a rapid non-genomic component involving membrane phenomena, such as alteration of membrane ionic permeability and activation of membrane-bound enzymes, as well as the classical genomic effect involving estrogen receptor activation and gene expression. Correspondence
Pharmacokinetics of telithromycin: application to dosing in the treatment of community-acquired respiratory tract infections

ABSTRACT Introduction: Telithromycin is the first ketolide antibacterial approved for treating community-acquired pneumonia, acute exacerbations of chronic bronchitis, and acute bacterial sinusitis in adults. The purpose of this article is to review the main pharmacokinetic properties of telithromycin and their application to the treatment of these infections. Methods: Sources of information were identified through a Medline search (up to March 2005). Main findings: The absolute oral bioavailability of telithromycin is ≈ 57%, which is unaffected by food intake. At the recommended 800 mg once-daily oral dosing regimen, telithromycin reaches a steady-state concentration of ≈ 2 µg/mL in plasma and has an elimination half-life of ≈ 10 hours. Telithromycin shows extensive tissue distribution and penetrates effectively into bronchopulmonary tissue and epithelial lining fluid. Since elimination of telithromycin occurs via multiple pathways – the highest proportion (70%) through metabolism – impairment of a single pathway has a limited impact on telithromycin exposure. Dose adjustments are unnecessary in elderly patients or in individuals with hepatic impairment or mild to moderate renal impairment. A reduced dose could be recommended in patients with severe renal impairment. Telithromycin is metabolized primarily in the liver, approximately half of which is via the cytochrome P450 (CYP) 3A4 system. Telithromycin AUC(0–24 h) increased by 1.5- to 2.0‐fold in the presence of itraconazole and ketoconazole. Administration of telithromycin with drugs metabolized via CYP3A4 may result in increased exposure to the co-administered drug, as shown for simvastatin (5.3‐fold) and midazolam (6‐fold). Co-administration of telithromycin minimally increases (1.2- to 1.4‐fold) exposure to theophylline, digoxin, and metoprolol. Although telithromycin does not affect the pharmacokinetics of warfarin, consideration should be given to monitoring prothrombin times/INR in patients receiving telithromycin and oral anticoagulants simultaneously. Conclusion: Overall, the pharmacokinetic/pharmacodynamic properties of telithromycin indicate that this ketolide antibacterial is a valuable and convenient treatment option for community-acquired respiratory tract infections.
Neither lymphotoxin α nor lymphotoxin β receptor expression is required for biogenesis of lymphoid aggregates or differentiation of natural killer cells in the pregnant mouse uterus

Gene ablation studies in mice indicate that lymphotoxin (LT)α, LTβ and LTβR are essential for the genesis of lymph nodes (LN), normal structural development of peripheral lymphoid tissues and the differentiation of natural killer (NK) cells. LTβR binds to the heterotrimeric cytokines LTα1β2 and LIGHT. LTs also regulate stromal cell expression of lymphocyte homing chemokines. Uterine decidualization in normal (+/+) mice is accompanied by the appearance and maturation of large numbers of uterine NK (uNK) cells that differentiate from precursors mobilized to the uterus from secondary lymphoid tissues. uNK cells accumulate in a transient, lymphocyte‐rich region known as the metrial gland or, more recently, the mesometrial lymphoid aggregrate of pregnancy (MLAp). To determine if LTs contribute to development of the MLAp, and to the differentiation and/or localization of uNK cells, a histological study was undertaken of implantation sites from LTα null, LTβR null and gestation day‐matched, normal mice. Implantation sites from the gene‐ablated mice contained abundant numbers of uNK cells that localized appropriately. This indicates that the stromally derived molecules supporting NK cell differentiation in the uterus differ from those used in secondary lymphoid organs.
Right hemisphere activation in recovery from aphasia

Background: Some neuroimaging studies have suggested that specific right hemispheric regions can compensate deficits induced by left hemispheric lesions in vascular aphasia. In particular, the right inferior frontal cortex might take part in lexical retrieval in patients presenting left-sided lesions involving the homologous area. Objective: To address whether the involvement of the right inferior frontal cortex is either unique to recovering aphasic patients or present also in other circumstances of enrichment of lexical abilities, i.e., in non–brain-damaged subjects over learning of new vocabulary. Methods: Ten post-stroke aphasic patients experiencing word finding difficulties were intensively trained to retrieve object names in French over a 4-week period. Twenty healthy subjects were similarly trained to name these items in either Spanish or English, i.e., foreign languages that they learned at school but did not master. By analogy to aphasic patients, healthy subjects had to work out the phonetic/phonologic representations of long-acquired but forgotten words. Brain activity changes were assessed in two H215O PET sessions involving picture naming tasks that were performed before and after training. Results: Comparable post-training performance and changes in regional cerebral blood flow including mainly the right insular and inferior frontal regions were found in both groups. Conclusion: Our results suggest that enhanced activities in right-sided areas observed in recovering aphasia is not the mere consequence of damage to left-sided homologous areas and could reflect the neural correlates of lexical learning also observed in control subjects.
Longitudinal analysis of behavioral, neurophysiological, viral and immunological effects of SIV infection in rhesus monkeys

Abstract: A model is proposed in which a neurovirulent, microglial‐passaged, simian immunodeficiency virus (SIV) is used to produce central nervous system (CNS) pathology and behavioral deficits in rhesus monkeys reminiscent of those seen in humans infected with human immunodeficiency virus (HIV). The time course of disease progression was characterized by using functional measures of cognition and motor skill, as well as neurophysiologic monitoring. Concomitant assessment of immunological and virological parameters illustrated correspondence between impaired behavioral performance and viral pathogenesis. Convergent results were obtained from neuropathological findings indicative of significant CNS disease. In ongoing studies, this SIV model is being used to explore the behavioral sequelae of immunodeficiency virus infection, the viral and host factors leading to neurologic dysfunction, and to begin testing potential therapeutic agents.
Antiepileptic drug use of women with epilepsy and congenital malformations in offspring

Objective: To compare the risk for congenital malformations in offspring between women with epilepsy being treated with antiepileptic drugs (AEDs) during pregnancy and those who discontinued their antiepileptic medication before pregnancy in a population-based cohort of female patients with epilepsy. Methods: All patients with epilepsy (n = 20,101) eligible for AED reimbursement for the first time during 1985 to 1994 were identified from the Social Insurance Institution of Finland. Information on births during 1991 to 2000 was obtained from the National Medical Birth Registry. Information on AED use during pregnancy and on pregnancy outcomes was abstracted from medical records. Results: Congenital malformations were more common among offspring of women on antiepileptic medication (65/1,411; 4.6%) than among offspring of untreated patients (26/939; 2.8%) (p = 0.02). The risk of malformations was substantially higher in the offspring of patients using valproate as monotherapy (OR = 4.18; 95% CI: 2.31, 7.57) or valproate as polytherapy (OR = 3.54; 95% CI: 1.42, 8.11) than of untreated patients. Polytherapy without valproate was not associated with increased risk of malformations. Conclusion: Excess risk was confined to patients using valproate during pregnancy. The risk for malformations was not elevated in offspring of mothers using carbamazepine, oxcarbazepine, or phenytoin (as monotherapy or polytherapy without valproate).
Contributions of mesozooplankton to vertical carbon export in a coastal upwelling system

Mesozooplankton can directly impact global biogeochemical cycles by repackaging particulate organic carbon (POC) into dense, rapidly sinking fecal pellets and by undertaking ver- tical migrations that transport carbon and nutrients to depth. We assessed these contributions of mesozooplankton to vertical flux in the California Current Ecosystem, a productive but spatiotem- porally variable coastal upwelling system, during cruises in April 2007 and October 2008. Sedi- ment traps and Thorium-234 ( 234 Th) disequilibrium measurements were used to assess the total passive flux of sinking POC, while pigment analyses and microscopic enumeration of sediment trap samples provided estimates of total fecal carbon transport. Identification of mesozooplankton in paired day-night, vertically stratified plankton tows allowed calculation of the active transport of carbon by the dominant taxa of vertically migrating mesozooplankton (particularly copepods and euphausiids). Across the range of 9 ecosystem conditions encountered on the cruises, recog- nizable fecal pellet mass flux varied from 3.5 to 135 mg C m �2 d �1 (3 to 94% of total passive flux) at the 100 m depth horizon. The active transport of carbon by migratory mesozooplankton taxa contributed an additional 2.4 to 47.1 mg C m �2 d �1 (1.9 to 40.5% of total passive flux). Inter-cruise comparisons suggest that fecal pellets contributed a higher portion of passive export during the productive spring cruise, when fecal material may have been responsible for close to 100% of sinking material. During the fall cruise, a gradient was observed with carbon export in productive water parcels driven by a large contribution of fecal pellets. In the less productive regions, fall ver- tical fluxes contained a higher proportion of marine snow and unidentifiable particles.
Ledging and blockage of root canals during canal preparation: causes, recognition, prevention, management, and outcomes

Ledge formation, that is the iatrogenically created irregularity in the root canal that impedes access of instruments to the apex, and canal blockage caused by packing dentin chips and/or tissue debris are the least-studied parameters of root canal instrumentation. Variables associated with ledge formation and canal blockage by dentin chips and/or tissue debris are presented. Emphasis is given to their most common causes, recognition, management, prognosis, and prevention.
Cryptosporidium spp. and cryptosporidiosis.

INTRODUCTION. 458 THE ORGANISM. 459 History . 459 Classification. 459 Host Specificity. 460 Life Cycle. 460 Morphology.463 THE HOSTS. 463 Infection in Fish and Snakes. 463 Infection in Birds. 464 Infection in Small Mammals. 464 Mice. 464 Rats . 465 Rabbits. 465 Guinea pigs. 465 Cats. 465 Dogs. 465 Squirrels and raccoons . 465 Infection in Large Mammals. 465 Nondomesticated ruminants. 465 Horses. 465 Pigs.466. Sheep. 466 Goats . 466 Cattle.466 Infection in Nonhuman Primates . 467 Infection in Humans . 467 History . 467 Geographic distribution and prevalence . 467 Age and sex distribution . 470 Clinical features. 470 Pathological features. 471 Transmission. 472 Immune response . 473 DIAGNOSIS . 473 EXPERIMENTAL. 475 Animal Models . 475 Cross-Transmission . 475 Virulence. 475 Oocyst and Sporozoite Isolation. 475 Excystation. 475 Cultivation. 476 TREATMENT AND CONTROL . 476 Treatment . 476 Control.477 ACKNOWLEDGMENTS. 477 LITERATURE CITED. 477
Comparative DNA binding of polynuclear aromatic hydrocarbons and their dihydrodiol and bay region diolepoxide metabolites in newborn mouse lung and liver.

Bay region diolepoxides of polynuclear aromatic hydrocarbons (PAHs) generally are more tumorigenic than their parent PAHs in newborn mice. This contrasts to the results obtained in mouse skin, in which the same diolepoxides are frequently less tumorigenic than their parents. In order to evaluate mechanism(s) responsible for this behavior we have investigated the binding of metabolites of [3H]benzo[a]pyrene (B[a]), [3H]5- and [3H6]6-methyl-chrysene (5-MeC and 6-MeC) and their corresponding dihydrodiols and bay region diolepoxides to pulmonary and hepatic DNA in male and female newborn mice and compared the results with their tumorigenic activities. Groups of 1 day old mice were treated with 0.4 or 4 nmol of the appropriate compounds in DMSO by i.p. injection. HPLC analysis of DNA hydrolysates obtained 24 h after treatment indicated that levels of diolepoxide-DNA adducts following treatment with (+-)-[3H]7,8-dihydroxy-7,8-dihydroB[a]P and (+-)-[3H]anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydroB[a] P are 5- and 10-fold higher than those formed from [3H]B[a]P. The major products (70-80%) released upon enzymatic hydrolysis of DNA following treatment with [3H]B[a]P, [3H]5-MeC and [3H]6-MeC were unidentified polar compounds. Levels of these unknown products were lower and formation of diolepoxide--DNA adducts higher when test compounds were changed from parent PAHs to the corresponding dihydrodiols and diolepoxides. Comparison of these results with those of tumorigenesis studies indicates a correlation between formation of B[a]P-diolepoxide--DNA adducts and induction of tumors in newborn mouse lung, but not in liver. These observations are consistent with the high sensitivity of the newborn mouse lung towards the tumorigenic effects of bay region diolepoxides. Previous studies have demonstrated that 1R,2S-dihydroxy-3S,4R,epoxy, 1,2,3,4-tetrahydro-5-MeC (5-MeC-1R,2S-diol-3S,4R-epoxide) is a potent lung tumorigen while the corresponding diol-epoxide of 6-MeC had no effect in newborn mice. From the results of the present study, we estimate that at equimolar doses the formation of diolepoxide--DNA adducts from 5-MeC-1R,2S-diol-3S,4R-epoxide would be at least 20-fold greater than from the corresponding diolepoxide of 6-MeC in newborn mouse lung. Thus, the higher tumorigenic activity of 5-MeC-1R,2S-diol-3S,4R-epoxide compared to that of the corresponding diol epoxide of 6-MeC is partially due to its greater extent of DNA damage.