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1
Blake, Timo, Anne Barnard, Stephen J. W. Busby, and Jeffrey Green. "Transcription Activation by FNR: Evidence for a Functional Activating Region 2." Journal of Bacteriology 184, no. 21 (November 1, 2002): 5855–61. http://dx.doi.org/10.1128/jb.184.21.5855-5861.2002.
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ABSTRACT The FNR protein of Escherichia coli controls the transcription of target genes in response to anoxia via the assembly-disassembly of oxygen-labile iron-sulfur clusters. Previous work identified patches of surface-exposed amino acids (designated activating regions 1 and 3 [AR1 and AR3, respectively]) of FNR which allow it to communicate with RNA polymerase (RNAP) and thereby activate transcription. Previously it was thought that FNR lacks a functional activating region 2 (AR2), although selecting for mutations that compensate for defective AR1 or a miscoordinated iron-sulfur cluster can reactivate AR2. Here we show that the substitution of two surface-exposed lysine residues (Lys49 and Lys50) of FNR impaired transcription from class II (FNR box centered at −41.5) but not class I (FNR box centered at −71.5) FNR-dependent promoters. The degree of impairment was greater when a negatively charged residue (Glu) replaced either Lys49 or Lys50 than when uncharged amino acid Ala was substituted. Oriented heterodimers were used to show that only the downstream subunit of the FNR dimer was affected by the Lys→Ala substitutions at a class II promoter. Site-directed mutagenesis of a negatively charged patch (162EEDE165) within the N-terminal domain of the RNAP α subunit that interacts with the positively charged AR2 of the cyclic AMP receptor protein suggested that Lys49 and Lys50 of FNR interact with this region of the α subunit of RNAP. Thus, it was suggested that Lys49 and Lys50 form part of a functional AR2 in FNR.
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Wetchapit, Pattarat, Usanee Tungsattayathitthan, Sutasinee Boonsopon, Nattaporn Tesavibul, and Pitipol Choopong. "Acute Retinal Necrosis: A Review of Diagnosis and Management." Siriraj Medical Journal 76, no. 10 (October 1, 2024): 727–32. http://dx.doi.org/10.33192/smj.v76i10.268914.
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Acute retinal necrosis (ARN) is a profound infection of the retina, marked by acute panuveitis, retinal periarteritis, and widespread necrotizing retinitis. The etiology of ARN involves human herpesviruses, such as herpes simplex virus (HSV) and varicella-zoster virus (VZV), which can lead to severe visual impairment or even blindness. A diagnosis of ARN is based on clinical characteristics and disease progression according to the standard diagnostic criteria established by the American Uveitis Society (AUS) in 1994. The polymerase chain reaction(PCR) of aqueous specimens can enable identification of the type of virus. Early initiation of antiviral medication is essential for treatment efficacy to stop lesion progression, accelerate the healing process, and prevent contralateral eye involvement. Ocular complications of ARN include atrophic retina, multiple retinal breaks, rhegmatogenous retinal detachment (RRD), tractional retinal detachment (TRD), optic atrophy, macular edema, epiretinal membrane (ERM), and retinal and optic disc neovascularization. This review summarizes the clinical features, diagnostic criteria, and recently recommended ARN management.
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Oe, Chiaki, Miki Hiraoka, Sachie Tanaka, and Hiroshi Ohguro. "Acute Retinal Necrosis Associated with Epstein-Barr Virus in a Patient Undergoing Immunosuppressive Therapy." Case Reports in Ophthalmology 7, no. 1 (April 12, 2016): 195–201. http://dx.doi.org/10.1159/000445372.
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Acute retinal necrosis (ARN) is a rapidly progressive and severe retinitis resulting in a poor visual outcome. Infections caused by herpes viruses such as herpes simplex virus (HSV) types 1 and 2 or the varicella zoster virus (VZV) are known to be implicated in the development of ARN. In the present study, an 80-year-old female with ARN was examined. She had been affected with rheumatoid arthritis and had taken methotrexate for over 10 years. Her right eye showed clinical features of ARN, and her left eye showed mild retinitis. The genomic DNA in the aqueous humor and vitreous fluid from her right eye were analyzed by a comprehensive polymerase chain reaction (PCR) assay to screen infectious pathogens including viruses. The Epstein-Barr virus (EBV) was detected from both specimens, but neither HSV or VZV nor cytomegalovirus was detected. She underwent intraocular surgery following systemic corticosteroid and acyclovir applications. However, although the retinitis of her right eye was extinguished, the final visual outcome was blindness due to optic nerve atrophy. There are few reports indicating that EBV is associated with ARN development. The present findings suggest that EBV alone can be the causative agent of ARN.
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Chujo, Shinichiro, Hisashi Matsubara, Yoshitusgu Matsui, Kumiko Kato, and Mineo Kondo. "Case of acute retinal necrosis with rapid progression to proliferative vitreoretinopathy: A case report." Medicine 103, no. 20 (May 17, 2024): e38150. http://dx.doi.org/10.1097/md.0000000000038150.
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Rationale: Acute retinal necrosis (ARN) was first reported in 1971 by Urayama et al as an acute uveitis accompanied by retinal arteritis and white retinal lesions in the peripheral retina that can progress to a rhegmatogenous retinal detachment (RRD). We have experienced a case of ARN that, unlike the common developmental course to an RRD associated with ARN, progressed to proliferative vitreoretinopathy (PVR) involving the entire retina in 2 days. The purpose of this report is to present our findings in the case of ARN with an atypical rapid time course. Patient concerns: The patient was a 56-year-old woman who was treated for uveitis of unknown origin by her primary care physician. She was referred to our hospital because of a worsening of the fundus findings. Diagnosis: Fundus examination in our hospital revealed vitreous opacities in the right eye, yellowish-white lesions extending around the retina, and some retinal hemorrhages. Because the retinal changes suggested ARN, we performed a polymerase chain reaction of the anterior atrial fluid and detected varicella-zoster virus. Then, the diagnosis of ARN was confirmed, and treatment was begun. At 1 month and a half after beginning the treatment, focal retinal traction was observed in the right fundus. Two days later, a circumferential PVR and a total retinal detachment were detected. Interventions: We then performed vitrectomy with an encircling buckle and a silicone oil tamponade. Outcomes: Our examination 6 months postoperatively showed that the retina was attached and the BCVA was 20/200. Lessons: Our findings of a case of ARN showed that the progression from a local vitreous traction to a full circumferential PVR can develop in 2 days.
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Yip, Siew Hoong, Ulrich Boehm, Allan E. Herbison, and Rebecca E. Campbell. "Conditional Viral Tract Tracing Delineates the Projections of the Distinct Kisspeptin Neuron Populations to Gonadotropin-Releasing Hormone (GnRH) Neurons in the Mouse." Endocrinology 156, no. 7 (April 9, 2015): 2582–94. http://dx.doi.org/10.1210/en.2015-1131.
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Kisspeptin neurons play an essential role in the regulation of fertility through direct regulation of the GnRH neurons. However, the relative contributions of the two functionally distinct kisspeptin neuron subpopulations to this critical regulation are not fully understood. Here we analyzed the specific projection patterns of kisspeptin neurons originating from either the rostral periventricular nucleus of the third ventricle (RP3V) or the arcuate nucleus (ARN) using a cell-specific, viral-mediated tract-tracing approach. We stereotaxically injected a Cre-dependent recombinant adenovirus encoding farnesylated enhanced green fluorescent protein into the ARN or RP3V of adult male and female mice expressing Cre recombinase in kisspeptin neurons. Fibers from ARN kisspeptin neurons projected widely; however, we did not find any evidence for direct contact with GnRH neuron somata or proximal dendrites in either sex. In contrast, we identified RP3V kisspeptin fibers in close contact with GnRH neuron somata and dendrites in both sexes. Fibers originating from both the RP3V and ARN were observed in close contact with distal GnRH neuron processes in the ARN and in the lateral and internal aspects of the median eminence. Furthermore, GnRH nerve terminals were found in close contact with the proximal dendrites of ARN kisspeptin neurons in the ARN, and ARN kisspeptin fibers were found contacting RP3V kisspeptin neurons in both sexes. Together these data delineate selective zones of kisspeptin neuron inputs to GnRH neurons and demonstrate complex interconnections between the distinct kisspeptin populations and GnRH neurons.
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Liu, Xinhuai, and Allan Herbison. "Kisspeptin Regulation of Arcuate Neuron Excitability in Kisspeptin Receptor Knockout Mice." Endocrinology 156, no. 5 (March 10, 2015): 1815–27. http://dx.doi.org/10.1210/en.2014-1845.
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The G protein-coupled receptor 54 (GPR54) is critical for kisspeptin to activate GnRH neurons to modulate fertility. However, the often mismatching distribution of kisspeptin and GPR54 in the brain suggests that kisspeptin may also act on other receptors. The arcuate nucleus (ARN) is one brain region with a very high density of kisspeptin fibers but only limited evidence for the expression of GPR54. Using acute brain slice electrophysiology in combination with Gpr54 knockout (GPR54KO) mouse models, we examined whether actions of kisspeptin in the ARN were dependent upon GPR54. Cell-attached recordings from unidentified ARN neurons in wild-type mice revealed that approximately one third of neurons were either excited or inhibited by kisspeptin in a dose-dependent manner. The responses of ARN neurons to kisspeptin were exactly the same in GPR54KO mice despite effects of kisspeptin on GnRH neurons being abolished. To evaluate whether kisspeptin may be acting through neuropeptide FF receptors, the effects of an agonist RFamide-related peptide 3 (RFRP-3) and antagonists RF9 and BIBP-3226 were evaluated. Both the excitatory and inhibitory effects of kisspeptin were mimicked by the agonist RFRP-3. RF9 itself activated ARN neurons and suppressed only the inhibitory actions of kisspeptin. BIBP-3226 suppressed kisspeptin actions in 50% of neurons. Whole-cell recordings in GPR54KO mice demonstrated that both kisspeptin and RFRP-3 acted directly on the same ARN neurons and activated the same ion channels. Together, these studies demonstrate that kisspeptin can act partly through neuropeptide FF receptors to modulate neuronal activity independent of GPR54 in the mouse brain.
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Keorochana, Narumon, Budsarat Suleesathira, and Sritatath Vongkulsiri. "Pigmentary retinopathy and nodular granuloma associated with acute retinal necrosis from varicella zoster virus and human herpes virus type 6: Case report." Medicine 102, no. 26 (June 30, 2023): e33958. http://dx.doi.org/10.1097/md.0000000000033958.
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Rationale: Acute retinal necrosis (ARN) caused by human herpes virus type 6 (HHV-6) is uncommon. We described a case of consecutive bilateral ARN, which was found to be a coinfection of varicella zoster virus (VZV) and HHV-6 in a 50-year-old woman, not well responded with systemic acyclovir. We showed the atypical findings with corresponding fundus and optical coherence tomography imaging. Patient concerns: She presented with anterior segment inflammation with peripheral retinitis and vasculitis in the left eye with disease progression despite of initial antiviral treatment, end up with retinal detachment. The right eye, subsequently, developed focal retinitis. Diagnosis: ARN was diagnosed by clinical fundus picture, confirmed by polymerase chain reaction (PCR). Interventions: Initially, she was treated with intravenous acyclovir and intravitreal ganciclovir for left eye. Retinal necrosis progressed, followed by retinal detachment. Pars plana vitrectomy with silicone oil was performed. The right eye, subsequently, developed focal retinitis. Medication was switched to intravenous ganciclovir and then oral valganciclovir. Outcomes: Retinitis was resolved, generalized hyperpigmentation appeared as a salt-and-pepper appearance in the right eye. The left eye presented preretinal deposits on silicone-retina interphase along retinal vessels. Spectral-domain optical coherence tomography (SD-OCT) showed multiple hyperreflective nodules on retinal surface. Lessons: ARN from coinfection of VZV and HHV-6 is rare. Preretinal granulomas and generalized hyperpigmentation could be one of the HHV-6 features. HHV-6 should be in the differential diagnosis for ARN. It responds well to systemic ganciclovir.
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Yeo, Shel-Hwa, and Allan E. Herbison. "Estrogen-Negative Feedback and Estrous Cyclicity Are Critically Dependent Upon Estrogen Receptor-α Expression in the Arcuate Nucleus of Adult Female Mice." Endocrinology 155, no. 8 (August 1, 2014): 2986–95. http://dx.doi.org/10.1210/en.2014-1128.
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The location and characteristics of cells within the brain that suppress GnRH neuron activity to contribute to the estrogen-negative feedback mechanism are poorly understood. Using adeno-associated virus (AAV)-mediated Cre-LoxP recombination in estrogen receptor-α (ERα) floxed mice (ERαflox/flox), we aimed to examine the role of ERα-expressing neurons located in the arcuate nucleus (ARN) in the estrogen-negative feedback mechanism. Bilateral injection of AAV-Cre into the ARN of ERαflox/flox mice (n = 14) resulted in the time-dependent ablation of up to 99% of ERα-immunoreactive cell numbers throughout the rostrocaudal length of the ARN. These mice were all acyclic by 5 weeks after AAV-Cre injections with most mice in constant estrous. Control wild-type mice injected with AAV-Cre (n = 13) were normal. Body weight was not altered in ERαflox/flox mice. After ovariectomy, a significant increment in LH secretion was observed in all genotypes, although its magnitude was reduced in ERαflox/flox mice. Acute and chronic estrogen-negative feedback were assessed by administering 17β-estradiol to mice as a bolus (LH measured 3 h later) or SILASTIC brand capsule implant (LH measured 5 d later). This demonstrated that chronic estrogen feedback was absent in ERαflox/flox mice, whereas the acute feedback was normal. These results reveal a critical role for ERα-expressing cells within the ARN in both estrous cyclicity and the chronic estrogen negative feedback mechanism in female mice. This suggests that ARN cells provide a key indirect, transsynpatic route through which estradiol suppresses the activity of GnRH neurons.
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Pan, Junhua, Vikram N. Vakharia, and Yizhi Jane Tao. "The structure of a birnavirus polymerase reveals a distinct active site topology." Proceedings of the National Academy of Sciences 104, no. 18 (April 24, 2007): 7385–90. http://dx.doi.org/10.1073/pnas.0611599104.
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Single-subunit polymerases are universally encoded in both cellular organisms and viruses. Their three-dimensional structures have the shape of a right-hand with the active site located in the palm region, which has a topology similar to that of the RNA recognition motif (RRM) found in many RNA-binding proteins. Considering that polymerases have well conserved structures, it was surprising that the RNA-dependent RNA polymerases from birnaviruses, a group of dsRNA viruses, have their catalytic motifs arranged in a permuted order in sequence. Here we report the 2.5 Å structure of a birnavirus VP1 in which the polymerase palm subdomain adopts a new active site topology that has not been previously observed in other polymerases. In addition, the polymerase motif C of VP1 has the sequence of -ADN-, a highly unusual feature for RNA-dependent polymerases. Through site-directed mutagenesis, we have shown that changing the VP1 motif C from -ADN- to -GDD- results in a mutant with an increased RNA synthesis activity. Our results indicate that the active site topology of VP1 may represent a newly developed branch in polymerase evolution, and that birnaviruses may have acquired the -ADN- mutation to control their growth rate.
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Sato, Tomohito, Wataru Yamamoto, Atsushi Tanaka, Haruna Shimazaki, Sunao Sugita, Toshikatsu Kaburaki, and Masaru Takeuchi. "Viral Loads in Ocular Fluids of Acute Retinal Necrosis Eyes Infected by Varicella-Zoster Virus Treated with Intravenous Acyclovir Treatment." Journal of Clinical Medicine 9, no. 4 (April 22, 2020): 1204. http://dx.doi.org/10.3390/jcm9041204.
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Acute retinal necrosis (ARN) is a rare viral endophthalmitis, and human herpesvirus is the principal pathogen. Early diagnosis and treatment are critical to avoid visual impairment by ARN, and pars plana vitrectomy (PPV) is required in advanced cases. In this study, we evaluated the transition of viral load in ocular fluids of ARN eyes with varicella-zoster virus (VZV) after intravenous acyclovir treatment. Fourteen eyes of 13 patients were analyzed retrospectively. All patients received intravenous acyclovir treatment, and eventually, all eyes underwent PPV. A polymerase chain reaction (PCR) test showed a 100% detection rate in all aqueous humor samples collected before the treatment (Pre-AH), as well as aqueous humor (Post-AH) and vitreous fluid samples (VF), collected during PPV conducted after the treatment. Within eight days or less of acyclovir treatment, viral loads both in AH and VF did not decrease significantly. Furthermore, the viral load of Pre-AH had a strong correlation with that of VH. These data suggest that in ARN eyes with VZV infection, the AH sample for the PCR test was reliable to confirm the pathogen. We propose that short-term treatment of intravenous acyclovir may be insufficient for reducing intraocular viral load, and the Pre-AH sample could be a predictor of viral activity in the eyes after acyclovir treatment.
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MONTI, SALVATORE, FRANCO DI SILVERIO, VINCENZO TOSCANO, CHIARA MARTINI, STEFANIA LANZARA, PAOLA A. VARASANO, and FRANCESCO SCIARRA. "Androgen Concentrations and Their Receptors in the Periurethral Region Are Higher Than Those of the Subcapsular Zone in Benign Prostatic Hyperplasia (BPH)." Journal of Andrology 19, no. 4 (July 8, 1998): 428–33. http://dx.doi.org/10.1002/j.1939-4640.1998.tb02036.x.
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ABSTRACT: Benign prostatic hyperplasia (BPH) is an androgen‐dependent disease that initially develops in the inner prostate, where the highest concentrations of testosterone (T) and dihydrotestosterone (DHT) are found. In this study, we have evaluated the cytosolic androgen receptors (ARc), the nuclear androgen receptors (ARn), and the concentrations of T, DHT, and 3α‐androstanediol (3αDiol) in BPH tissue to verify the existence of a possible correlation between androgens and their receptor concentrations. Prostatic samples, removed by suprapubic prostatectomy in 15 untreated patients, were sectioned in periurethral, intermediate, and subcapsular zones. Testosterone, DHT, and 3αDiol were evaluated by radioimmunoassay after extraction and purification on celite microcolumns, and ARc and ARn were evaluated by means of dextran‐coated charcoal method. In total tissue, mean levels of DHT, T, and 3αDiol were 2,531 ± 308, 260 ± 36, and 403 ± 35 pg/mg of DNA (mean ± SE), respectively. Cytosolic androgen receptors, detectable in all cases, were 16 ± 2.8 fmol/mg of protein (mean ± SE), and ARn, detectable in 12 cases, were 108 ± 15 fmol/mg of DNA (mean ± SE). A linear correlation between DHT and 3αDiol, T and DHT, and 3aDiol and ARn was found. If the different regions are considered, the periurethral zone, site of the primitive BPH nodule, presents the highest levels of androgens and ARn with respect to the other regions. This relative hyperandrogenism may be responsible for the growth‐promoting processes of this area, leading to urinary obstruction.
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Medipally, Ajay, Min Xiao, Anjali A. Satoskar, Laura Biederman, Iouri Ivanov, Galina Mikhalina, and Sergey Brodsky. "Research Letter: Is the 129S1/SvImJ Mouse Strain More Suitable to Study Anticoagulant-Related Nephropathy Than the C57BL/6 Strain?" Canadian Journal of Kidney Health and Disease 10 (January 2023): 205435812311605. http://dx.doi.org/10.1177/20543581231160507.
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Background: We have previously demonstrated that excessive anticoagulation with warfarin or dabigatran may result in acute kidney injury with red blood cell (RBC) tubular casts in some patients with chronic kidney disease, and this condition was named anticoagulant-related nephropathy (ARN). 5/6 nephrectomy (5/6NE) rats treated with warfarin or dabigatran reproduce the main pathologic features of human ARN. We had reported that 5/6NE C57BL/6 mice only partially develop ARN with increased serum creatinine and hematuria but no RBC tubular casts in the kidney. Objectives: The aim of this study was to investigate whether ARN can develop in 5/6NE 129S1/SvImJ mice. Methods: 5/6NE was performed in 129S1/SvImJ mice. Three weeks after 5/6NE, mice were treated with warfarin (1.0 and 1.5 mg/kg/day) or vehicle for 7 days. Serum creatinine, hematuria, and prothrombin time (PT) were monitored daily. Renal morphology was evaluated at the end of the studies. Results: Treatment with warfarin resulted in PT elevation 2 to 3 folds from baseline (1.0 mg/kg/day warfarin) and 4 to 5 folds from baseline (1.5 mg/kg/day warfarin) by day 7. Serum creatinine and hematuria elevated by day 7 in a dose-dependent manner. Histologically, 2 of 8 (25%) 5/6NE mice had RBCs in the tubules, and there was acute tubular epithelial cell injury in all warfarin-treated 5/6NE 129S1/SvImJ mice. Conclusions: Our findings suggest that 129S1/SvImJ mouse strain is a more suitable murine model to study ARN than C57BL/6 mouse strain.
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Baumgartner, Valentin, Dominik Schaer, Daniel Eberli, and Souzan Salemi. "Targeting Metabolic Vulnerabilities to Overcome Prostate Cancer Resistance: Dual Therapy with Apalutamide and Complex I Inhibition." Cancers 15, no. 23 (November 28, 2023): 5612. http://dx.doi.org/10.3390/cancers15235612.
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Prostate cancer (PCa) often becomes drug-treatment-resistant, posing a significant challenge to effective management. Although initial treatment with androgen deprivation therapy can control advanced PCa, subsequent resistance mechanisms allow tumor cells to continue growing, necessitating alternative approaches. This study delves into the specific metabolic dependencies of different PCa subtypes and explores the potential synergistic effects of combining androgen receptor (AR) inhibition (ARN with mitochondrial complex I inhibition (IACS)). We examined the metabolic behaviors of normal prostate epithelial cells (PNT1A), androgen-sensitive cells (LNCaP and C4-2), and androgen-independent cells (PC-3) when treated with ARN, IACS, or a combination. The results uncovered distinct mitochondrial activities across PCa subtypes, with androgen-dependent cells exhibiting heightened oxidative phosphorylation (OXPHOS). The combination of ARN and IACS significantly curbed cell proliferation in multiple PCa cell lines. Cellular bioenergetics analysis revealed that IACS reduced OXPHOS, while ARN hindered glycolysis in certain PCa cells. Additionally, galactose supplementation disrupted compensatory glycolytic mechanisms induced by metabolic reprogramming. Notably, glucose-deprived conditions heightened the sensitivity of PCa cells to mitochondrial inhibition, especially in the resistant PC-3 cells. Overall, this study illuminates the intricate interplay between AR signaling, metabolic adaptations, and treatment resistance in PCa. The findings offer valuable insights into subtype-specific metabolic profiles and propose a promising strategy to target PCa cells by exploiting their metabolic vulnerabilities.
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Rathkopf, Dana E., Michael J. Morris, Daniel Costin Danila, Susan F. Slovin, Jill Elise Steinbrecher, Gabrielle Arauz, Tracy Curley, et al. "A phase I study of the androgen signaling inhibitor ARN-509 in patients with metastatic castration-resistant prostate cancer (mCRPC)." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): 4548. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.4548.
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4548 Background: ARN-509 is a novel small molecule AR antagonist that impairs AR nuclear translocation and binding to DNA, inhibiting tumor growth and promoting apoptosis, with no partial agonist activity. (Clegg et al., 2012) We conducted a phase I trial to assess safety, pharmacokinetics (PK), and determine the recommended phase II dose (RP2D). Methods: Eligible patients with mCRPC received ARN-509 orally on a continuous daily dosing schedule. Seven doses (30, 60, 90, 120, 180, 240, and 300 mg) were tested using standard 3x3 dose escalation criteria. Once drug concentrations were achieved that met or exceeded optimal levels predicted preclinically, an additional 2 dose levels were tested to further confirm the safety margin of ARN-509 (390 and 480 mg). Anti-tumor activity was assessed by PSA, radiographic responses, and FDHT-PET imaging. Results: Thirty patients were enrolled. The most common grades 1-2 treatment-related adverse events were fatigue (38%), nausea (29%), and pain (24%). There was only 1 treatment-related grade 3 adverse event (abdominal pain) at 300 mg, possibly related to a higher pill burden. PK was shown to be linear and dose-dependent. At 12 weeks, 42% of patients have had ≥ 50% PSA declines. Eleven (37%) patients have discontinued the study due to progression, with the longest patient still on study for more than 16 months. FDHT-PET imaging demonstrated AR blockade at 4 weeks across multiple dose levels. Conclusions: In this phase I study, ARN-509 was shown to be safe and well tolerated with linear PK. Based on promising activity across all dose levels and pharmacodynamic evidence of AR antagonism, an optimal biologic dose of 240 mg daily was selected for phase II investigation. DOD/PCF PCCTC trial sponsored by Aragon Pharmaceuticals.
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Attoui, H., F. Mohd Jaafar, S. Maan, and P. P. C. Mertens. "Génétique inverse pour les virus à ARN à double brin." Revue d’élevage et de médecine vétérinaire des pays tropicaux 62, no. 2-4 (February 1, 2009): 150. http://dx.doi.org/10.19182/remvt.10059.
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Since the recognition by Sabin of the specific nature of reoviruses in 1959 and the characterisation of their genome as double-stranded ribonucleic acid (dsRNA) by Gomatos in 1960, there have been many attempts to rescue viruses by transfecting cells with viral dsRNA. These attempts were largely unsuccessful. In 1990, it was proposed by Roner and Joklik that messenger (m) RNA transcribed from orthoreovirus cores was infectious when that mRNA was transfected into cells together with rabbit reticulocyte lysates that were pre-incubated with denatured viral dsRNAs. However, attempts to reproduce these ‘rescue’ experiments failed in the hands of other scientists. A breakthrough came in 2007 when Kobayashi and Dermody established a plasmid-based reverse genetics system for the orthoreoviruses, which represents the first reliable, synthetic based, reverse genetic system for a dsRNA virus. The system made it possible to study the role of specified amino acids in the outer capsid protein by generating ‘designer’ mutants. A second and potentially even more significant breakthrough came in the same year when Boyce and Roy showed that mRNA transcribed from the bluetongue virus core was infectious, allowing rescue of the virus in BSR cells, a clone of BHK-21 cells. This same group extended their work to the generation of synthetic transcripts from complementary (c) DNA copies of each of the 10 genome segments cloned into plasmids, driven by the T7 polymerase. We report refinement of a T7 base transcription approach, which uses simple linear polymerase chain reaction (PCR) amplicons of the individual virus genome segments from any reovirus, for transcription of full length, fully capped mRNA transcripts. These transcripts were used to transfect BSR cells and permitted rescue of the corresponding viruses. There was no requirement for a second transfection of either capped or uncapped messages. The efficiency of the system was significantly improved, using modulators of the cells’ innate immunity; particularly, 2-aminopurine considerably enhanced the rescue and shortened the time for appearance of lysis plaques. This system was successfully used for 12 segmented coltiviruses, the 12 segmented seadornaviruses and 10 segmented orbiviruses. The authors suggest that this simplified rescue-strategy should be applicable to any dsRNA virus, particularly the members of the 15 recognized genera of the family Reoviridae. The system is currently being tested for mono-partite dsRNA viral genomes.
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Dorman, Andrew, and Mark Donaldson. "Acute Retinal Necrosis Multicenter Case Series: Prognostic Indicators and Treatment Outcomes." Journal of VitreoRetinal Diseases 2, no. 6 (September 19, 2018): 327–37. http://dx.doi.org/10.1177/2474126418798559.
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Purpose: The purpose of this article is to report the prognostic associations of acute retinal necrosis (ARN), determine the diagnostic utility of aqueous vs vitreous polymerase chain reaction (PCR), and describe outcomes of antiviral, corticosteroid, antithrombotic, and laser retinopexy treatment. Methods: A retrospective, nonrandomized case series was conducted. Primary outcomes included final visual acuity (VA), severe VA loss (≥1.00 log of the minimum angle of resolution [logMAR] [Snellen equivalent, <20/200]), and retinal detachment (RD). Results: Fifty eyes of 46 patients were diagnosed with ARN. Varicella-zoster and herpes simplex viruses were the viral etiology in 29 and 16 eyes, respectively. Five were diagnosed on clinical criteria. Intravenous acyclovir was administered in 90% of eyes. Neither induction therapy for ≥13 days ( P = .692) nor intravitreal medication ( P = .203) decreased the incidence of severe vision loss. Maintenance antiviral medication was administered in 96% of eyes (50% received >13 weeks). At final follow-up, 40% of eyes had severe vision loss (range, –0.08 to +3.0 logMAR [Snellen, 20/17-no perception of light]). Forty-six percent developed RD. Relative afferent pupillary defect (RAPD), zone and extent of retinitis, and RD were prognostic of final VA. Antithrombotic therapy was administered in 25/50 eyes and was associated with lower incidence of severe VA loss ( P = .027) and better final VA ( P = .040). Laser retinopexy was performed in 40% of eyes with no significant effect on RD incidence ( P = .901) or severe VA loss ( P = .451). Conclusions: ARN has a high incidence of RD and poor visual outcomes. Aqueous humor PCR is the first-line diagnostic investigation. Prognostic indicators include RD, RAPD, zone, and extent of retinitis. Induction antiviral medication is appropriate for at least 12 days. Antithrombotic medication is associated with improved outcomes. Laser retinopexy does not reduce the incidence of RD.
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Faber, J. E., and D. R. Gettes. "Renal pressor reflex: involvement of sympathetic vasoconstrictor mechanisms." American Journal of Physiology-Heart and Circulatory Physiology 252, no. 6 (June 1, 1987): H1147—H1158. http://dx.doi.org/10.1152/ajpheart.1987.252.6.h1147.
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We examined whether vasopressin and/or sympathetic vasoconstrictor mechanisms constitute the efferent limb of an afferent renal nerve (ARN)-dependent renal pressor "reflex" produced by acute unilateral renal artery stenosis (RST). Rats that had received sinoaortic denervation (SAD) were implanted with right renal artery occluders and flow probes. After recovery, conscious rats received captopril. Acute RST increased arterial pressure (AP) by 25% and mesenteric and hindquarters resistances by 35 and 51%, respectively. Vasopressin receptor antagonism was without effect on the reflex. Ganglionic blockade (chlorisondamine or trimethaphan) abolished the reflex, as did alfaxalone/alfadolone or urethan-chloralose anesthesia. In an additional study, SAD animals were prepared with chronic T6 spinal cord transection. Increases in AP during RST were unaffected by spinal transection (27 +/- 4 mmHg). However, the increase in hindquarter resistance in the sham-transected animals (57 +/- 12%) was markedly attenuated (19 +/- 4%) in the spinal-transected group. The data suggest that in animals with depressed baroreflexes and renin-angiotensin system responsiveness, acute RST initiates an ARN-dependent pressor reflex with vasoconstrictor nerves comprising the efferent limb of the reflex. The reflex can be integrated at the spinal level and is highly sensitive to anesthesia.
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Rathkopf, Dana E., Daniel Costin Danila, Michael J. Morris, Susan F. Slovin, Jill Elise Steinbrecher, Gabrielle Arauz, Peter J. Rix, et al. "Phase I/II safety and pharmacokinetic (PK) study of ARN-509 in patients with metastatic castration-resistant prostate cancer (mCRPC): Phase I results of a Prostate Cancer Clinical Trials Consortium study." Journal of Clinical Oncology 30, no. 5_suppl (February 10, 2012): 43. http://dx.doi.org/10.1200/jco.2012.30.5_suppl.43.
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43 Background: In CRPC, androgen receptor (AR) overexpression is associated with resistance to first-generation anti-androgen therapy such as bicalutamide. ARN-509 is a novel small molecule AR antagonist that impairs AR nuclear translocation and binding to DNA, inhibiting tumor growth and promoting apoptosis, with no partial agonist activity. Preclinical data shows that ARN-509 binds AR with 5-fold greater affinity than bicalutamide, and induces tumor regression in hormone-sensitive and CRPC xenograft models. Methods: In this open-label, Phase 1/2 study, mCRPC patients received ARN-509 orally on a continuous daily dosing schedule. In Phase 1 , 7 doses (30, 60, 90, 120, 180, 240, 300 mg) were tested using standard 3x3 dose escalation criteria to assess safety, PK, and determine the recommended Phase 2 dose (RP2D). Preliminary anti-tumor activity was assessed by PSA kinetics, radiographic responses, circulating tumor cells (CTCs), and FDHT-PET imaging. Results: Twenty-four patients (median age 68 yrs, Gleason Score 8; prior docetaxel 13%) were enrolled. The most common Grade 1-2 treatment-related adverse events were fatigue (38%), nausea (29%), and pain (24%). There was only 1 treatment-related Grade 3 adverse event (abdominal pain) at 300 mg, possibly related to a higher pill burden, which led to an additional 3 patients being enrolled at the highest dose with no further dose limiting toxicities. PK was shown to be linear and dose-dependent. Twelve patients (55%) had ≥ 50% PSA declines. To date, 7 patients have discontinued the study due to progression, with the longest patient still on study for more than 1 year. FDHT-PET imaging demonstrated AR blockade at 4 weeks across multiple dose levels. Based on preclinical assessment of maximum efficacious dose, PK, and promising activity across all doses, 240 mg was selected as the RP2D. Conclusions: In this Phase 1 study, ARN-509 was shown to be safe and well tolerated, with promising preliminary activity based on PSA and pharmacodynamic evidence of AR antagonism. The Phase 2 portion of the study will enroll up to 90 patients with treatment-naïve non-metastatic and mCRPC.
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Maroń, Anna M., Joanna Palion-Gazda, Agata Szłapa-Kula, Ewa Schab-Balcerzak, Mariola Siwy, Karolina Sulowska, Sebastian Maćkowski, and Barbara Machura. "Controlling of Photophysical Behavior of Rhenium(I) Complexes with 2,6-Di(thiazol-2-yl)pyridine-Based Ligands by Pendant π-Conjugated Aryl Groups." International Journal of Molecular Sciences 23, no. 19 (September 20, 2022): 11019. http://dx.doi.org/10.3390/ijms231911019.
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The structure–property correlations and control of electronic excited states in transition metal complexes (TMCs) are of high significance for TMC-based functional material development. Within these studies, a series of Re(I) carbonyl complexes with aryl-substituted 2,6-di(thiazol-2-yl)pyridines (Arn-dtpy) was synthesized, and their ground- and excited-state properties were investigated. A number of condensed aromatic rings, which function as the linking mode of the aryl substituent, play a fundamental role in controlling photophysics of the resulting [ReCl(CO)3(Arn-dtpy-κ2N)]. Photoexcitation of [ReCl(CO)3(Arn-dtpy-κ2N)] with 1-naphthyl-, 2-naphthyl-, 9-phenanthrenyl leads to the population of 3MLCT. The lowest triplet state of Re(I) chromophores bearing 9-anthryl, 2-anthryl, 1-pyrenyl groups is ligand localized. The rhenium(I) complex with appended 1-pyrenyl group features long-lived room temperature emission attributed to the equilibrium between 3MLCT and 3IL/3ILCT. The excited-state dynamics in complexes [ReCl(CO)3(9-anthryl-dtpy-κ2N)] and [ReCl(CO)3(2-anthryl-dtpy-κ2N)] is strongly dependent on the electronic coupling between anthracene and {ReCl(CO)3(dtpy-κ2N)}. Less steric hindrance between the chromophores in [ReCl(CO)3(2-anthryl-dtpy-κ2N)] is responsible for the faster formation of 3IL/3ILCT and larger contribution of 3ILCTanthracene→dtpy in relation to the isomeric complex [ReCl(CO)3(9-anthryl-dtpy-κ2N)]. In agreement with stronger electronic communication between the aryl and Re(I) coordination centre, [ReCl(CO)3(2-anthryl-dtpy-κ2N)] displays room-temperature emission contributed to by 3MLCT and 3ILanthracene/3ILCTanthracene→dtpy phosphorescence. The latter presents rarely observed phenomena in luminescent metal complexes.
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Attenni, Barbara, Salvatore Avolio, Stefania Colarusso, Savina Malancona, Steven Harper, Sergio Altamura, Uwe Koch, and Frank Narjes. "Inhibitors of the hepatitis C virus RNA-dependent RNA polymerase." Arkivoc 2006, no. 7 (March 19, 2006): 479–95. http://dx.doi.org/10.3998/ark.5550190.0007.733.
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Joseph, A. A., and A. H. Fagbami. "Coronaviruses: a review of their properties and diversity." African Journal of Clinical and Experimental Microbiology 21, no. 4 (August 25, 2020): 258–71. http://dx.doi.org/10.4314/ajcem.v21i4.2.
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Human coronaviruses, which hitherto were causative agents of mild respiratory diseases of man, have recently become one of the most important groups of pathogens of humans the world over. In less than two decades, three members of the group, severe acute respiratory syndrome (SARS) coronavirus (CoV), Middle East respiratory syndrome (MERS)-CoV, and SARS-COV-2, have emerged causing disease outbreaks that affected millions and claimed the lives of thousands of people. In 2017, another coronavirus, the swine acute diarrhea syndrome (SADS) coronavirus (SADS-CoV) emerged in animals killing over 24,000 piglets in China. Because of the medical and veterinary importance of coronaviruses, we carried out a review of available literature and summarized the current information on their properties and diversity. Coronaviruses are single-stranded RNA viruses with some unique characteristics such as the possession of a very large nucleic acid, high infidelity of the RNA-dependent polymerase, and high rate of mutation and recombination in the genome. They are susceptible to a number of physical agents and several chemical agents used for disinfection procedures in hospitals and laboratories. They exhibit considerable genetic and host diversity, causing diseases of gastrointestinal and respiratory system in a wide range of vertebrate hosts including humans. The high prevalence of coronaviruses in domestic and wild animals, especially bats and birds, and the propensity for their genomes to undergo mutation and recombination may lead to emergence of new coronaviruses that could pose a serious threat to human and animal health.
Keywords: coronaviruses; SARS-CoV; MERS-CoV; SARS-Cov-2; properties; diversity; review
French Title: Coronavirus: revue de leurs propriétés et de leur diversité
Les coronavirus humains, qui étaient jusqu'à présent des agents responsables de maladies respiratoires bénignes de l'homme, sont récemment devenus l'un des groupes les plus importants d'agents pathogènes humains dans le monde entier. En moins de deux décennies, trois membres du groupe, le coronavirus (CoV) du syndrome respiratoire aigu sévère (SRAS), le syndrome respiratoire du Moyen-Orient (MERS)-CoV et le SRAS-COV-2, sont apparus, provoquant des épidémies qui ont touché des millions et des personnes. a coûté la vie à des milliers de personnes. En 2017, un autre coronavirus, le coronavirus du syndrome de la diarrhée aiguë du porc (SADS) (SADS-CoV) est apparu chez des animaux tuant plus de 24000 porcelets en Chine. En raison de l'importance médicale et vétérinaire des coronavirus, nous avons effectué une revue de la littérature disponible et résumé les informations actuelles sur leurs propriétés et leur diversité. Les coronavirus sont des virus à ARN simple brin avec certaines caractéristiques uniques telles que la possession d'un très grand acide nucléique, une infidélité élevée de la polymérase dépendante de l'ARN, et un taux élevé de mutation et de recombinaison dans le génome. Ils sont sensibles à un certain nombre d'agents physiques et à plusieurs agents chimiques utilisés pour les procédures de désinfection dans les hôpitaux et les laboratoires. Ils présentent une diversité génétique et hôte considérable, provoquant des maladies du système gastro-intestinal et respiratoire dans un large éventail d'hôtes vertébrés, y compris les humains. La forte prévalence des coronavirus chez les animaux domestiques et sauvages, en particulier les chauves-souris et les oiseaux, et la propension de leurs génomes à subir des mutations et des recombinaisons peuvent conduire à l'émergence de nouveaux coronavirus qui pourraient constituer une menace sérieuse pour la santé humaine et animale.
Mots-clés: coronavirus; SARS-CoV; MERS-CoV; SRAS-CoV-2; Propriétés; la diversité; la revue
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Cobilinschi, Claudia, Cristian Cobilinschi, Alexandra Constantinescu, Ruxandra Ionescu, and Daniela Opris-Belinski. "Scleroderma renal crisis as the sole presenting feature of systemic sclerosis in a postpartum woman." Romanian Journal of Rheumatology 30, no. 2 (June 30, 2021): 83–87. http://dx.doi.org/10.37897/rjr.2021.2.6.
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Systemic sclerosis is a chronic autoimmune disorder characterized by multiorgan involvement, most notably of the skin through fibrosis and vasculopathy. One of its most feared complications requiring rapid intervention is scleroderma renal crisis, as it can be fatal in the absence of prompt treatment. A 34-year old woman presents with a history of acute renal failure and malignant hypertension occurring one month postpartum and no other scleroderma feature in the following 5 years. Eventually, skin, heart and lung involvement is observed, positive anti-ARN III polymerase antibodies and suggestive capillaroscopic findings. Immunosuppressive therapy with mycophenolate mofetil is initiated and later switched to off-label Rituximab, with significant improvement of disease manifestations. Regular patient monitoring for novel symptom occurrence and appropriate treatment adjustment is essential for optimal management of scleroderma.
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Sullivan, K. O., and Gregory I. Gellene. "Ab initio study of Arn–HCO+ (n = 0–6): insight into size dependent cluster ion properties." International Journal of Mass Spectrometry 201, no. 1-3 (July 2000): 121–34. http://dx.doi.org/10.1016/s1387-3806(00)00217-7.
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Bergemann, S. E., and M. Garbelotto. "High diversity of fungi recovered from the roots of mature tanoak (Lithocarpus densiflorus) in northern California." Canadian Journal of Botany 84, no. 9 (September 2006): 1380–94. http://dx.doi.org/10.1139/b06-097.
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We collected mature tanoak ( Lithocarpus densiflorus (Hook. & Arn.) Rehder) roots from five stands to characterize the relative abundance and taxonomic richness of root-associated fungi. Fungi were identified using polymerase chain reaction (PCR), cloning, and sequencing of internal transcribed spacer (ITS) and 28S rDNA. A total of 382 cloned PCR inserts were successfully sequenced and then classified into 119 taxa. Of these taxa, 82 were basidiomycetes, 33 were ascomycetes, and 4 were zygomycetes. Thirty-one of the ascomycete sequences were identified as Cenococcum geophilum Fr. with overall richness of 22 ITS types. Other ascomycetes that form mycorrhizal associations were identified including Wilcoxina and Tuber as well as endophytes such as Lachnum , Cadophora , Phialophora , and Phialocephela . The most abundant mycorrhizal groups were Russulaceae ( Lactarius , Macowanites , Russula ) and species in the Thelephorales ( Bankera , Boletopsis , Hydnellum , Tomentella ). Our study demonstrates that tanoak supports a high diversity of ectomycorrhizal fungi with comparable species richness to that observed in Quercus root communities.
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Widhodho, Joko, Elly Proklamasiningsih, and Pudji Widodo. "RESPON AKAR KIARA PAYUNG (Filicium decipiens (Wight & Arn.) Thwaites) PADA KONDISI CEKAMAN NATRIUM HIPOKLORIT." VIGOR: JURNAL ILMU PERTANIAN TROPIKA DAN SUBTROPIKA 7, no. 2 (December 31, 2022): 47–56. http://dx.doi.org/10.31002/vigor.v7i2.6706.
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Sodium hypochlorite (NaClO) was a chemical compound commonly used as a whitening and disinfectant agent. Kiara payung (Filicium decipiens), or the ferntree, was chosen as the object of research because easily obtained, has rapid growth, and thought to respond to alien substances' stress. The main purpose of this study was to find out the response of the ferntree plant, which is given stress from sodium hypochlorite. The research method used in this study was experimentation. The independent variable in this study was Sodium Hypochlorite Concentration (X), and the dependent variable was Sodium Hypochlorite Uptake Value (Y). Phytochemical analysis was performed using the argentometry and Atomic Absorption Spectrophotometry (AAS) techniques. Correlation analysis were performed using IBM SPSS 26. This study showed that the concentration of sodium hypochlorite has a positive effect on the uptake value of sodium hypochlorite. Limitations and suggestions to this study were to check the absorption based on soil level and examine other parts of the plant in the future study. In addition, another factors to the independent variables, such as genetics and variations in sodium hypochlorite concentration should be further explored, so that correlation analysis stands more optimal. Keywords: Ferntree, Root, Sodium Hypochlorite, Stress
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Phan, Thanh Nam, Okwha Kim, Manh Tuan Ha, Cheol Hwangbo, Byung-Sun Min, and Jeong-Hyung Lee. "Albanol B from Mulberries Exerts Anti-Cancer Effect through Mitochondria ROS Production in Lung Cancer Cells and Suppresses In Vivo Tumor Growth." International Journal of Molecular Sciences 21, no. 24 (December 14, 2020): 9502. http://dx.doi.org/10.3390/ijms21249502.
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Albanol B (ABN-B), an arylbenzofuran derivative isolated from mulberries, has been shown to have anti-Alzheimer’s disease, anti-bacterial and antioxidant activities. The aim of this study was to investigate the anti-cancer effect of this compound against lung cancer cells. The results show that ABN-B inhibited the proliferation of four human lung cancer cell lines (A549, BZR, H1975, and H226) and induced apoptosis, based on the cleavage of caspase-7 and PARP (poly (ADP-ribose) polymerase), as well as the downregulation of Bcl-2. ABN-B also induced cell cycle arrest at G2/M by down-regulating the expression of CKD1 (cyclin-dependent kinase 1) and cyclin B1, but up-regulating p21 (cyclin-dependent kinase inhibitor 1) expression. Notably, ABN-B increased the production of mitochondrial reactive oxygen species (ROS); however, treatment with mito-TEMPO (a specific mitochondrial antioxidant) blocked ABN-B-induced cell cycle arrest at G2/M and apoptosis, as well as the up-regulation of p21 and down-regulation of CDK1 and cyclin B1 induced by ABN-B. At the molecular level, ABN-B-induced mitochondrial ROS production increased the phosphorylation levels of AKT (protein kinase B) and ERK1/2 (extracellular signal-regulated kinase 1/2), while the inhibition of these kinases blocked the ABN-B-induced up-regulation of p21 and down-regulation of CDK1 and cyclin B1. Moreover, ABN-B significantly suppressed tumor growth in Ex-3LL (Lewis lung carcinoma) tumor-bearing mice. Taken together, these results suggest that ABN-B can exert an anti-cancer effect by inducing apoptosis and cell cycle arrest at G2/M through mitochondrial ROS production in lung cancer cells.
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Crater, Dinene L., and Charles P. Moran. "Two Regions of GerE Required for Promoter Activation in Bacillus subtilis." Journal of Bacteriology 184, no. 1 (January 1, 2002): 241–49. http://dx.doi.org/10.1128/jb.184.1.241-249.2002.
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ABSTRACT GerE from Bacillus subtilis is the smallest member of the LuxR-FixJ family of transcription activators. Its 74-amino-acid sequence is similar over its entire length to the DNA binding domain of this protein family, including a putative helix-turn-helix (HTH) motif. In this report, we sought to define regions of GerE involved in promoter activation. We examined the effects of single alanine substitutions at 19 positions that were predicted by the crystal structure of GerE to be located on its surface. A single substitution of alanine for the phenylalanine at position 6 of GerE (F6A) resulted in decreased transcription in vivo and in vitro from the GerE-dependent cotC promoter. However, the F6A substitution had little effect on transcription from the GerE-dependent cotX promoter. In contrast, a single alanine substitution for the leucine at position 67 (L67A) reduced transcription from the cotX promoter, but not from the cotC promoter. The results of DNase I protection assays and in vitro transcription reactions lead us to suggest that the F6A and L67A substitutions define two regions of GerE, activation region 1 (AR1) and AR2, that are required for activation of the cotC and cotX promoters, respectively. A comparison of our results with those from studies of MalT and BvgA indicated that other members of the LuxR-FixJ family may use more than one surface to interact with RNA polymerase during promoter activation.
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Schmidt, Martin, Michel Mons, and Jacques Le Calvé. "Influence of Microsolvation on the Molecular Dynamics: Structure-Dependent Intramolecular Vibrational Redistribution Process in the Benzene-Arn Heteroclusters." Berichte der Bunsengesellschaft für physikalische Chemie 96, no. 9 (September 1992): 1284–87. http://dx.doi.org/10.1002/bbpc.19920960942.
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McCall, Andrew C. "Does dose-dependent petal damage affect pollen limitation in an annual plant?" Botany 88, no. 6 (June 2010): 601–6. http://dx.doi.org/10.1139/b10-032.
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Damage to flowers by herbivores, or florivory, can have direct impacts on gamete survival and can also indirectly affect fitness by reducing pollinator service. While recent studies have examined the impact of natural or artificial floral damage, very few researchers have manipulated both damage and pollen addition to see whether pollen limitation is enhanced by damage, and no workers, to my knowledge, have examined whether pollen limitation is dependent on the levels of florivory used. I used a pollen addition treatment and six levels of artificial floral damage to investigate whether damage increases pollen limitation and whether that pollen limitation becomes more severe with increasing numbers of petals damaged in Nemophila menziesii Hook. & Arn. I found that artificial floral damage that mimics natural florivore damage increases pollen limitation, and that this pollen limitation generally increased with increasing numbers of petals damaged. The treatment with the heaviest amount of damage did not suffer the most pollen limitation, perhaps because flowers in this treatment remained radially symmetric. These findings suggest that florivory may decrease pollen import through pollinator deterrence and could thus serve as a selective force on either floral or defense traits in outcrossing plant populations.
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Sobanski, V., L. Dauchet, G. Lefèvre, M. Lambert, S. Morell-Dubois, T. Sy, E. Hachulla, P. Y. Hatron, D. Launay, and S. Dubucquoi. "Prévalence des anticorps anti-ARN polymerase de type III dans la sclérodermie systémique : nouvelle cohorte française, revue systématique et méta-analyse." La Revue de Médecine Interne 34 (December 2013): A34—A35. http://dx.doi.org/10.1016/j.revmed.2013.10.040.
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Thi Dung, Luu, Doan Huu Thien, Nguyen Thi Ly, Nguyen Thi Hong Dinh, Be Thi Tham, Nguyen Hoang Tung, and Pham Van Hung. "RT-PCR test for specific indentification of influenzavirus (A/H5N1) in vaccine." JOURNAL OF CONTROL VACCINES AND BIOLOGICALS, no. 1 (December 31, 2021): 66–77. http://dx.doi.org/10.56086/jcvb.vi1.6.
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RT-PCR (Reverse transcription - Polymerase Chain Reaction) is applied to determine the presence of influenza virus A/ H5N1 in vaccine, and to develop an identity process for specific virus strain A/H5N1 in influenza vaccine A/H5N1. Selected samples included: Ivacflu-A/H5N1 vaccine (Institute of Vaccines and Biologicals), Vaxigrip vaccine (Sanofi Pasteur), Influenza virus strain A/ Vietnam/1194/2004(A/H5N1) (NIBSC) was used as positive control; vaccine Varivax (MSD) and DNA/RNA free water was used as negative controls. The results showed that virus strain A/H5N1 was identified as production of RT-PCR that were positive with amplified primer pairs of 2 specific gene sequences of HA whose length 428 and 249 bp. Before starting RT-PCR, it was necessary to eliminate aluminum and the components of RT-PCR reaction included: 5X QIAGEN OneStep RT-PCR Buffer(5µl); dNTP (1µl); forward and reverse primers (1,5 µl); Enzyme (1 µl), H2 O (10 µl), ARN template (5 µl) and thermal cycle of RT- PCR reaction was: 50oC (30 minutes); 95OC (15 minutes); 94OC (30 seconds); 55OC (30 seconds); 72OC (1 minute); 72OC (10 minutes), 45 cycles.
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Wall, Stephanie B., Rui Li, Brittany Butler, Ashley R. Burg, Hubert M. Tse, Jennifer L. Larson-Casey, A. Brent Carter, Clyde J. Wright, Lynette K. Rogers, and Trent E. Tipple. "Auranofin-Mediated NRF2 Induction Attenuates Interleukin 1 Beta Expression in Alveolar Macrophages." Antioxidants 10, no. 5 (April 21, 2021): 632. http://dx.doi.org/10.3390/antiox10050632.
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Background: Alveolar macrophages (AMs) are resident inflammatory cells in the lung that serve as early sentinels of infection or injury. We have identified thioredoxin reductase 1 inhibition by gold compounds increases activation of nuclear factor erythroid 2-related factor 2 (NRF2)-dependent pathways to attenuate inflammatory responses. The present studies utilized murine alveolar macrophages (MH-S) to test the hypothesis that the gold compound, auranofin (AFN), decreases interleukin (IL)-1β expression through NRF2-mediated interactions with nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway genes and/or increases in glutathione synthesis. Methods: MH-S cells were treated with AFN and lipopolysaccharide (LPS) and analyzed at 6 and 24 h. The Il1b promoter was analyzed by chromatin immunoprecipitation for direct interaction with NRF2. Results: Expression of IL-1β, p-IκBα, p-p65 NF-kB, and NOD-, LRR-, and pyrin domain-containing protein 3 were elevated by LPS exposure, but only IL-1β expression was suppressed by AFN treatment. Both AFN and LPS treatments increased cellular glutathione levels, but attenuation of glutathione synthesis by buthionine sulfoximine (BSO) did not alter expression of Il-1β. Analysis revealed direct NRF2 binding to the Il1b promoter which was enhanced by AFN and inhibited the transcriptional activity of DNA polymerase II. Conclusions: Our data demonstrate that AFN-induced NRF2 activation directly suppresses IL-1β synthesis independent of NFκB and glutathione-mediated antioxidant mechanisms. NRF2 binding to the promoter region of IL1β directly inhibits transcription of the IL1β gene. Collectively, our research suggests that gold compounds elicit NRF2-dependent pulmonary protection by suppressing macrophage-mediated inflammation.
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Chen, Zhuo, David Holec, Matthias Bartosik, Paul H. Mayrhofer, and Zaoli Zhang. "Crystallographic orientation dependent maximum layer thickness of cubic AlN in CrN/AlN multilayers." Acta Materialia 168 (April 2019): 190–202. http://dx.doi.org/10.1016/j.actamat.2019.02.004.
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Stone, Robert Douglas, and Quentin Luke. "Lijndenia udzungwarum (Melastomataceae–Olisbeoideae): a new, endemic species from the Udzungwa Mountains of southern Tanzania." Phytotaxa 226, no. 2 (September 11, 2015): 169. http://dx.doi.org/10.11646/phytotaxa.226.2.6.
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Lijndenia udzungwarum R.D. Stone & Q. Luke, a shrub or small tree of Tanzania’s Udzungwa Mountains, is described and illustrated. The placement of the new species in Lijndenia is indicated by its trinervate, papillose-muricate leaves and persistent bracteoles partially fused to form a cupule immediately subtending each flower. The cordate leaves of L. udzungwarum are unique in the genus. From the East African L. brenanii (A. Fern. & R. Fern.) Jacq.-Fél. and L. procteri (A. Fern. & R. Fern.) Borhidi, the new species is further distinguished by its capitellate inflorescences on long, filiform, axillary peduncles, resembling those of the Sri Lankan L. capitellata (Arn.) K. Bremer. Despite its local endemism, L. udzungwarum has been assessed as ‘Least Concern’ according to IUCN criteria, although this assessment is dependent on the continued safeguarding of the Udzungwa Mountains National Park. An identification key is provided for the three currently recognized Tanzanian species of Lijndenia.
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Huang, Yong-Heng, Nelly Said, Bernhard Loll, and Markus C. Wahl. "Structural basis for the function of SuhB as a transcription factor in ribosomal RNA synthesis." Nucleic Acids Research 47, no. 12 (April 25, 2019): 6488–503. http://dx.doi.org/10.1093/nar/gkz290.
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AbstractRibosomal RNA synthesis in Escherichia coli involves a transcription complex, in which RNA polymerase is modified by a signal element on the transcript, Nus factors A, B, E and G, ribosomal protein S4 and inositol mono-phosphatase SuhB. This complex is resistant to ρ-dependent termination and facilitates ribosomal RNA folding, maturation and subunit assembly. The functional contributions of SuhB and their structural bases are presently unclear. We show that SuhB directly binds the RNA signal element and the C-terminal AR2 domain of NusA, and we delineate the atomic basis of the latter interaction by macromolecular crystallography. SuhB recruitment to a ribosomal RNA transcription complex depends on the RNA signal element but not on the NusA AR2 domain. SuhB in turn is required for stable integration of the NusB/E dimer into the complex. In vitro transcription assays revealed that SuhB is crucial for delaying or suppressing ρ-dependent termination, that SuhB also can reduce intrinsic termination, and that SuhB-AR2 contacts contribute to these effects. Together, our results reveal functions of SuhB during ribosomal RNA synthesis and delineate some of the underlying molecular interactions.
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Lai, Cheng-Yuan, Ming-Chun Hsieh, Yu-Cheng Ho, An-Sheng Lee, Hsueh-Hsiao Wang, Jen-Kun Cheng, Yat-Pang Chau, and Hsien-Yu Peng. "Growth Arrest and DNA-damage–inducible Protein 45β-mediated DNA Demethylation of Voltage-dependent T-type Calcium Channel 3.2 Subunit Enhances Neuropathic Allodynia after Nerve Injury in Rats." Anesthesiology 126, no. 6 (June 1, 2017): 1077–95. http://dx.doi.org/10.1097/aln.0000000000001610.
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Abstract Background Growth arrest and DNA-damage–inducible protein 45β reactivates methylation-silenced neural plasticity-associated genes through DNA demethylation. However, growth arrest and DNA-damage–inducible protein 45β–dependent demethylation contributes to neuropathic allodynia-associated spinal plasticity remains unclear. Methods Adult male Sprague–Dawley rats (654 out of 659) received a spinal nerve ligation or a sham operation with or without intrathecal application of one of the following: growth arrest and DNA-damage–inducible protein 45β messenger RNA–targeted small interfering RNA, lentiviral vector expressing growth arrest and DNA-damage–inducible protein 45β, Ro 25–6981 (an NR2B-bearing N-methyl-d-aspartate receptor antagonist), or KN-93 (a calmodulin-dependent protein kinase II antagonist) were used for behavioral measurements, Western blotting, immunofluorescence, dot blots, detection of unmodified cytosine enrichment at cytosine-phosphate-guanine site, chromatin immunoprecipitation quantitative polymerase chain reaction analysis, and slice recordings. Results Nerve ligation-enhanced growth arrest and DNA-damage–inducible protein 45β expression (n = 6) in ipsilateral dorsal horn neurons accompanied with behavioral allodynia (n = 7). Focal knockdown of growth arrest and DNA-damage–inducible protein 45β expression attenuated ligation-induced allodynia (n = 7) by reducing the binding of growth arrest and DNA-damage–inducible protein 45β to the voltage-dependent T-type calcium channel 3.2 subunit promoter (n = 6) that decreased expression of and current mediated by the voltage-dependent T-type calcium channel 3.2 subunit (both n = 6). In addition, NR2B-bearing N-methyl-d-aspartate receptors and calmodulin-dependent protein kinase II act in an upstream cascade to increase growth arrest and DNA-damage–inducible protein 45β expression, hence enhancing demethylation at the voltage-dependent T-type calcium channel 3.2 subunit promoter and up-regulating voltage-dependent T-type calcium channel 3.2 subunit expression. Intrathecal administration of Ro 25–6981, KN-93, or a growth arrest and DNA-damage–inducible protein 45β–targeting small interfering RNA (n = 6) reversed the ligation-induced enrichment of unmodified cytosine at the voltage-dependent T-type calcium channel 3.2 subunit promoter by increasing the associated 5-formylcytosine and 5-carboxylcytosine levels. Conclusions By converting 5-formylcytosine or 5-carboxylcytosine to unmodified cytosine, the NR2B-bearing N-methyl-d-aspartate receptor, calmodulin-dependent protein kinase II, or growth arrest and DNA-damage–inducible protein 45β pathway facilitates voltage-dependent T-type calcium channel 3.2 subunit gene demethylation to mediate neuropathic allodynia.
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Wulfert, Francis M., Matijs van Meurs, Neng F. Kurniati, Rianne M. Jongman, Martin C. Houwertjes, Peter Heeringa, Michel M. R. F. Struys, Jan G. Zijlstra, and Grietje Molema. "Age-dependent Role of Microvascular Endothelial and Polymorphonuclear Cells in Lipopolysaccharide-induced Acute Kidney Injury." Anesthesiology 117, no. 1 (July 1, 2012): 126–36. http://dx.doi.org/10.1097/aln.0b013e31825b57c9.
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Background The incidence of acute kidney injury following severe sepsis is higher in the elderly. We hypothesized that microvascular endothelium is "primed" by aging and that sepsis represents a "second hit," resulting in more severe microvascular complications. Methods Three- and 18-months-old mice were intraperitoneally injected with 1,500 EU/g body weight lipopolysaccharide and sacrificed after 8 h. Flow cytometry and myeloperoxidase ELISA determined neutrophils in plasma. Quantitative reverse transcription polymerase chain reaction was used to analyze messenger ribonucleic acid levels of cell adhesion molecules P-selectin and E-selectin, vascular cell adhesion protein-1, intercellular adhesion molecule-1, angiopoietin receptor TIE-2, and angiopoietins Ang1 and Ang2. In kidney tissue we assessed neutrophil influx and E-selectin protein expression. Neutrophils were depleted with the monoclonal antibody NIMP. Results At basal conditions, microvascular endothelial cell activation status was similar in both groups, except for a higher Ang-2 expression (P < 0.05) in the kidney of aged mice. Lipopolysaccharide-induced increase in neutrophil count was higher in old (3.3-fold change) compared with young mice (2.2-fold change). Messenger ribonucleic acid analysis showed higher upregulation of P- and E-selectin (P = 0.0004, P = 0.0007) after lipopolysaccharide administration in kidneys of elderly mice, which was confirmed at the protein level for E-selectin. Renal neutrophil influx in lipopolysaccharide-treated aged mice was increased (2.5-fold induction in aged and 2.1-fold in young, P < 0.0001). Polymorphonuclear cell depletion exaggerated the lipopolysaccharide-induced kidney injury. Conclusion Ang-2 is increased in older mice, which might cause priming of the endothelial cells. Endothelium responded by a more extensive increase in expression of P- and E-selectin in older mice and increased polymorphonuclear cell influx.
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Li, Dai, Zhen-Zhen Huang, Yun-Zhi Ling, Jia-You Wei, Yu Cui, Xiang-Zhong Zhang, He-Quan Zhu, and Wen-Jun Xin. "Up-regulation of CX3CL1 via Nuclear Factor-κB–dependent Histone Acetylation Is Involved in Paclitaxel-induced Peripheral Neuropathy." Anesthesiology 122, no. 5 (May 1, 2015): 1142–51. http://dx.doi.org/10.1097/aln.0000000000000560.
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Abstract Background: Up-regulation of CX3CL1 has been revealed to be involved in the neuropathic pain induced by nerve injury. However, whether CX3CL1 participates in the paclitaxel-induced painful peripheral neuropathy remains unknown. The aim of the current study was to elucidate the involvement of transcriptional factors nuclear factor-κB (NF-κB) and its causal interaction with CX3CL1 signaling in the paclitaxel-induced painful peripheral neuropathy. Methods: Painful peripheral neuropathy induced by paclitaxel treatment was established in adult male Sprague-Dawley rats. The von Frey test were performed to evaluate neuropathic pain behavior, and real-time quantitative reverse transcription polymerase chain reaction, chromatin immunoprecipitation, Western blot, immunohistochemistry, and small interfering RNA were performed to understand the molecular mechanisms. Results: The application of paclitaxel induced an up-regulation of CX3CL1 expression in the spinal neurons, which is reduced significantly by NF-κB inhibitor ammonium pyrrolidinedithiocarbamate or p65 small interfering RNA. Blockade of either CX3CL1 (n = 12 each) or NF-κB (n = 12 each) signaling pathway attenuated mechanical allodynia induced by paclitaxel. Chromatin immunoprecipitation further found that paclitaxel induced an increased recruitment of nuclear factor-κB (NF-κB)p65 to the Cx3cl1 promoter region. Furthermore, an increased acetylation level of H4, but not H3, in Cx3cl1 promoter region in spinal neurons was detected after paclitaxel treatment, which was reversed by inhibition of NF-κB with ammonium pyrrolidinedithiocarbamate or p65 small interfering RNA. Conclusions: These findings suggest that up-regulation of CX3CL1 via NF-κB–dependent H4 acetylation might be critical for paclitaxel-induced mechanical allodynia.
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Chen, D., X. L. Ma, and Y. M. Wang. "Thickness-dependent structural transformation in the AlN film." Acta Materialia 53, no. 19 (November 2005): 5223–27. http://dx.doi.org/10.1016/j.actamat.2005.08.003.
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Kaczorowska, Malgorzata, Szczepan Roszak, and Jerzy Leszczynski. "Are the Properties of Shells Ligand Dependent? An ab Initio Study of Mixed H3+Arn(H2)m(n+m= 6) Cations." Journal of Physical Chemistry A 105, no. 33 (August 2001): 7938–44. http://dx.doi.org/10.1021/jp011475v.
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Melkina, Olga E., Ignatiy I. Goryanin, and Gennadii B. Zavilgelsky. "The DNA–mimic antirestriction proteins ArdA ColIB-P9, Arn T4, and Ocr T7 as activators of H-NS-dependent gene transcription." Microbiological Research 192 (November 2016): 283–91. http://dx.doi.org/10.1016/j.micres.2016.07.008.
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RP, Malini, Betty T, Vasini V, and Sumathi P. "Evaluation of Carrageenan-induced Anti-inflammatory Activity of Ethanolic Leaf Extract of Psychotria bisulcata Wight &Arn. in Wistar Rats." UTTAR PRADESH JOURNAL OF ZOOLOGY 45, no. 21 (November 12, 2024): 23–33. http://dx.doi.org/10.56557/upjoz/2024/v45i214613.
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Psychotria bisulcata Wight & Arn. (Rubiaceae) is a shrub widely used in traditional medicine for the treatment of rheumatoid arthritis, diabetes, infertility and impotence. The present research work is focused on in vitro and in vivo anti-inflammatory activity in ethanolic leaf extract of P. bisulcata. The ethanol extract was subjected to in vitro anti-inflammatory assays such as hypotonic solution-induced hemolysis, heat-induced hemolysis. The in vitro anti-inflammatory assays revealed that the ethanolic leaf extract of P. bisulcata showed a high level of inhibition in hypotonic solution-induced hemolysis in 250 µg/mL as 55.80±1.91and in heat-induced hemolysis as 62.23±4.23. The in vivo anti-inflammatory activity was assessed using the carrageenan-induced paw edema model, with diclofenac as the standard. When compared to the standard diclofenac, the ethanolic leaf extract of P. bisulcata showed considerable anti-inflammatory efficacy in a dose dependent manner, resulting in the reduction of paw edema volume. The rats treated with ethanolic leaf extract of 500 mg/kg showed better activity. The research discovers that P. bisulcata has substantial anti-inflammatory action, indicating that it has medicinal potential in the treatment of inflammatory ailments.
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Song, Huayuan, Yuan Han, Cailong Pan, Xueting Deng, Wenling Dai, Liang Hu, Chunyi Jiang, et al. "Activation of Adenosine Monophosphate–activated Protein Kinase Suppresses Neuroinflammation and Ameliorates Bone Cancer Pain." Anesthesiology 123, no. 5 (November 1, 2015): 1170–85. http://dx.doi.org/10.1097/aln.0000000000000856.
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Abstract Background Activation of adenosine monophosphate–activated kinase (AMPK) has been associated with the inhibition of inflammatory nociception and the attenuation of morphine antinociceptive tolerance. In this study, the authors investigated the impact of AMPK activation through resveratrol treatment on bone cancer pain. Methods The nociception was assessed by measuring the incidence of foot withdrawal in response to mechanical indentation in rats (n = 8). Cytokine expression was measured using quantitative polymerase chain reaction (n = 8). Cell signalings were assayed by western blot (n = 4) and immunohistochemistry (n = 5). The microglial cell line BV-2, primary astrocytes, and neuron-like SH-SY5Y cells were cultured to investigate the in vitro effects. Results Resveratrol and 5-amino-1-β-d-ribofuranosyl-imidazole-4-carboxamide, the AMPK activators, significantly attenuated bone cancer pain in rats with tumor cell implantation (TCI; threshold of mechanical withdrawal, resveratrol vs. vehicle: 10.1 ± 0.56 vs. 4.1 ± 0.37; 5-amino-1-β-d-ribofuranosyl-imidazole-4-carboxamide vs. vehicle: 8.2 ± 0.17 vs. 4.1 ± 0.37, mean ± SEM); these effects were reversed by the AMPK inhibitor compound C (compound C vs. resveratrol: 6.2 ± 1.35 vs. 10.1 ± 0.56, mean ± SEM). Resveratrol has an AMPK-dependent inhibitory effect on TCI-evoked astrocyte and microglial activation. The antinociceptive effects of resveratrol were partially mediated by the reduced phosphorylation of mitogen-activated protein kinases and decreased production of proinflammatory cytokines in an AMPK-dependent manner. Furthermore, resveratrol potently inhibited inflammatory factors–mediated protein kinase B/mammalian target of rapamycin signaling in neurons. Acute pain evoked by proinflammatory cytokines in the spinal cord was significantly attenuated by resveratrol. Conclusions AMPK activation in the spinal glia by resveratrol may have utility in the treatment of TCI-induced neuroinflammation, and our results further implicate AMPK as a novel target for the attenuation of bone cancer pain.
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Fatima, Syeda, Nazia Aslam, Sofia Khalid, Kalim Ullah, Khizar Abbas, Shahzad Hussain, Syed Sajid Hussain Shah, Zia-Ur-Rahman Qureshi, Mughal Qayum, and Muhammad Hassham Hassan Bin Asad. "Antihyaluronidase and Alkaline Phosphatase (ALP) Activities of Medicinal Plants to Combat Echis carinatus Venom-Induced Toxicities." BioMed Research International 2021 (March 16, 2021): 1–8. http://dx.doi.org/10.1155/2021/6618349.
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Snakebite is one of the most neglected diseases of developing countries. Deaths due to snakebite envenoming are quite high in Pakistan, and many deaths are caused by Echis carinatus envenomation. Traditional use of medicinal plants against snakebites is a common practice in Pakistan due to countless benefits. The current study was performed with the objective to evaluate eighteen Pakistani medicinal plants inhibitory potential against hyaluronidase and alkaline phosphatase enzymes of Pakistani Echis carinatus venom. Hyaluronidase activity (0.2-1.6 mg/0.1 mL) and alkaline phosphatase activity (0.1-0.8 mg/0.1 mL) were measured in dose-dependent manner. Crude methanolic extracts of medicinal plants were used for in vitro investigation of their inhibitory activity against toxic enzymes. All active plants were fractioned using different solvents and were again analyzed for inhibitory activity of same enzymes. Results indicated all plants were able to neutralize hyaluronidase that Swertia chirayita (Roxb. ex Flem.) Karst., Terminalia arjuna Wight and Arn, Rubia cordifolia Thumb., and Matthiola incana (L.) R.Br. inhibited maximum hyaluronidase activity equivalent to standard reference ( p > 0.5 ). Pakistani medicinal plants are dense with natural neutralizing metabolites and other active phytochemicals which could inhibit hyaluronidase activity of Pakistani Echis carinatus venom. Further advanced studies at molecular level could lead us to an alternative for envenoming of Pakistani Echis carinatus venom.
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Leal, Sofia, Derek Eamus, Michael Grabner, Rupert Wimmer, and Paolo Cherubini. "Tree rings of Pinus nigra from the Vienna basin region (Austria) show evidence of change in climatic sensitivity in the late 20th century." Canadian Journal of Forest Research 38, no. 4 (April 2008): 744–59. http://dx.doi.org/10.1139/x07-189.
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The width of tree rings of Pinus nigra Arn. trees growing near the ecological limits for the species, in the Vienna basin, Austria, showed a strong and positive correlation with spring–summer precipitation, indicating a dependence of growth on water availability during the growing season. During the late 20th century, tree rings grew wider than expected given the predicted relationship between rainfall and growth rate observed in the early 20th century. This resulted in models of the relationship between climate and growth rate systematically overestimating the total spring–summer (April–July) precipitation over the last half of the 20th century. Analysis of the temporal stability of the relationship between tree growth and climate variables shows a decrease in the sensitivity of the growth of tree rings to spring–summer precipitation towards the end of the 20th century. This change in sensitivity suggests that tree growth was no longer primarily dependent on water availability. We propose that there was an improvement in water-use efficiency arising from a stimulation of photosynthesis and declining stomatal conductance as a consequence of the increasing CO2 concentration in the atmosphere and that this effect was enhanced by a relatively high input of N due to the proximity of N emission sources.
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Liang, De-Yong, XiangQi Li, and J. David Clark. "5-Hydroxytryptamine Type 3 Receptor Modulates Opioid-induced Hyperalgesia and Tolerance in Mice." Anesthesiology 114, no. 5 (May 1, 2011): 1180–89. http://dx.doi.org/10.1097/aln.0b013e31820efb19.
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Background Opioid-induced hyperalgesia (OIH) and tolerance are challenging maladaptations associated with opioids in managing pain. Recent genetic studies and the existing literature suggest the 5-hydroxytryptamine type 3 (5-HT3) receptor participates in these phenomena. The location of the relevant receptor populations and the interactions between the 5-HT3 system and other systems controlling OIH and tolerance have not been explored, however. We hypothesized that 5-HT3 receptors modulate OIH and tolerance, and that this modulation involves the control of expression of multiple neurotransmitter and receptor systems. Methods C57BL/6 mice were exposed to a standardized 4-day morphine administration protocol. The 5-HT3 antagonist ondansetron was administered either during or after the conclusion of morphine administration. Mechanical testing was used to quantify OIH, and thermal tail-flick responses were used to measure morphine tolerance. In other experiments spinal cord and dorsal root ganglion tissues were harvested for analysis of messenger RNA concentrations by real-time polymerase chain reaction or immunochemistry analysis. Results The results showed that (1) systemic or intrathecal injection of ondansetron significantly prevented and reversed OIH, but not local intraplantar injection; (2) systemic or intrathecal injection of ondansetron prevented and reversed tolerance; and (3) ondansetron blocked morphine-induced increases of multiple genes relevant to OIH and tolerance in dorsal root ganglion and spinal cord. Conclusions Morphine acts via a 5-HT3-dependent mechanism to support multiple maladaptations to the chronic administration of morphine. Furthermore, the use of 5-HT3 receptor antagonists may provide a new avenue to prevent or reverse OIH and tolerance associated with chronic opioid use.
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Zhang, Yan Ping, Ariel Eber, Yue Yuan, Zhe Yang, Yiliam Rodriguez, Roy C. Levitt, Peter Takacs, and Keith A. Candiotti. "Prophylactic and Antinociceptive Effects of Coenzyme Q10 on Diabetic Neuropathic Pain in a Mouse Model of Type 1 Diabetes." Anesthesiology 118, no. 4 (April 1, 2013): 945–54. http://dx.doi.org/10.1097/aln.0b013e3182829b7b.
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Abstract Background: Oxidative stress is a key factor implicated in the development of diabetic neuropathy. This study evaluates the prophylactic and antinociceptive effects of the antioxidant coenzyme Q10 (CoQ10) on diabetes-induced neuropathic pain in a diabetic mouse model. Methods: Total 56 mice with type 1 diabetes induced by streptozotocin were used, 20 normal mice were used as control. Mechanical and thermal nociceptive behavioral assays were applied to evaluate diabetic neuropathic pain. Tissue lipid peroxidation, immunohistochemistry, reverse transcription, and polymerase chain reaction were used to evaluate the molecular mechanisms of CoQ10. Data are presented as mean ± SEM. Results: CoQ10 administration was associated with reduced loss of body weight compared with nontreated diabetic mice, without affecting blood glucose levels. Low dose and long-term administration of CoQ10 prevented the development of neuropathic pain. Treatment with CoQ10 produced a significant dose-dependent inhibition of mechanical allodynia and thermal hyperalgesia in diabetic mice. Dorsal root ganglia, sciatic nerve, and spinal cord tissues from diabetic mice demonstrated increased lipid peroxidation that was reduced by CoQ10 treatment. CoQ10 administration was also noted to reduce the proinflammatory factors in the peripheral and central nervous system. Conclusions: The results of this study support the hypothesis that hyperglycemia induced neuronal oxidative damage and reactive inflammation may be pathogenic in diabetic neuropathic pain. CoQ10 may be protective by inhibiting oxidative stress and reducing inflammation by down-regulating proinflammatory factors. These results suggest that CoQ10 administration may represent a low-risk, high-reward strategy for preventing or treating diabetic neuropathy.
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Meiabadi, Mohammad Saleh, Mahmoud Moradi, Mojtaba Karamimoghadam, Sina Ardabili, Mahdi Bodaghi, Manouchehr Shokri, and Amir H. Mosavi. "Modeling the Producibility of 3D Printing in Polylactic Acid Using Artificial Neural Networks and Fused Filament Fabrication." Polymers 13, no. 19 (September 23, 2021): 3219. http://dx.doi.org/10.3390/polym13193219.
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Polylactic acid (PLA) is a highly applicable material that is used in 3D printers due to some significant features such as its deformation property and affordable cost. For improvement of the end-use quality, it is of significant importance to enhance the quality of fused filament fabrication (FFF)-printed objects in PLA. The purpose of this investigation was to boost toughness and to reduce the production cost of the FFF-printed tensile test samples with the desired part thickness. To remove the need for numerous and idle printing samples, the response surface method (RSM) was used. Statistical analysis was performed to deal with this concern by considering extruder temperature (ET), infill percentage (IP), and layer thickness (LT) as controlled factors. The artificial intelligence method of artificial neural network (ANN) and ANN-genetic algorithm (ANN-GA) were further developed to estimate the toughness, part thickness, and production-cost-dependent variables. Results were evaluated by correlation coefficient and RMSE values. According to the modeling results, ANN-GA as a hybrid machine learning (ML) technique could enhance the accuracy of modeling by about 7.5, 11.5, and 4.5% for toughness, part thickness, and production cost, respectively, in comparison with those for the single ANN method. On the other hand, the optimization results confirm that the optimized specimen is cost-effective and able to comparatively undergo deformation, which enables the usability of printed PLA objects.
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Prakash, Palanisamy, Ekambaram Gayathiri, Rengarajan Manivasagaperumal, and Patcharin Krutmuang. "Biological Activity of Root Extract Decalepishamiltonii (Wight & Arn) against Three Mosquito Vectors and Their Non-Toxicity against the Mosquito Predators." Agronomy 11, no. 7 (June 22, 2021): 1267. http://dx.doi.org/10.3390/agronomy11071267.
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Bioactive molecules of plant origin play a significant role as defensive agents in different insect species. Chemical compounds in medicinal plants have been an exciting alternative to standard methods of controlling mosquito larvae. The present study evaluates the different solvent extracts of D. hamiltonii for toxicity against three different mosquito larvae. Bioassay revealed that the effect of the methanol extracts increased the larval mortality with increasing concentration. The highest larval mortality was observed in Culex quinquefasciatus with 98.33%, followed by 95 and 90% mortality in Aedes aegypti and Anopheles stephensi, at 24 h exposure. GC-MS analysis of methanol extract of D. hamiltonii showed six major peak compounds. They are benzaldehyde, 2-hydroxy-4-methoxy-(10.35%), dodecanoic acid (11.02%), n-hexadecanoic acid (21.05%), linoleic acid methyl ester (14.20%), oleic acid (21.04%), octadecanoic acid (22.21%). The level of α and β Carboxylesterases gets significantly decreased post-treatment with the methanol extract of D. hamiltonii in a dose-dependent manner.In contrast, glutathione S-transferase (GST) and cytochrome-P450 (CYP450) levels get up-lifted steadily when the dosage gets increased. The ratio of GST level has drastically proclaimed to in Ae. aegypti 0.702 mg/m Lin parallel to Cx. quiquefasciatus (0.656 mg/mL) and An. stephensi (0.812 mg/mL). Cytochrome P450 (CYP450) activity was observed to increase significantly post-treatment with the sub-lethal dosage of methanol extract of D. hamiltonii. Correspondingly, the non-target screening against the aquatic predators reveals that the crude root extracts and their derivatives are ecologically safe and less toxic. Overall, the present research highlights the chemical characterization of crude methanol extracts of D. hamiltonii, their insecticidal activity against the medically challenging pests, and their non-target activity delivers an ecologically safe, and target specific bio-active agents and suitable substitute for chemical pesticides.
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Schäfer, Simon T., Lars Franken, Michael Adamzik, Beatrix Schumak, André Scherag, Andrea Engler, Niels Schönborn, et al. "Mitochondrial DNA." Anesthesiology 124, no. 4 (April 1, 2016): 923–33. http://dx.doi.org/10.1097/aln.0000000000001008.
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Abstract Background Critically ill patients are at high risk to suffer from sepsis, even in the absence of an initial infectious source, but the molecular mechanisms for their increased sepsis susceptibility, including a suppressed immune system, remain unclear. Although microbes and pathogen-associated molecular pattern are accepted inducers of sepsis and septic immunosuppression, the role of endogenous Toll-like receptor (TLR) ligands, such as mitochondrial DNA (mtDNA), in altering the immune response is unknown. Methods Mitochondrial DNA serum concentrations of the mitochondrial genes D-Loop and adenosine triphosphatase 6 were determined (quantitative polymerase chain reaction) in 165 septic patients and 50 healthy volunteers. Furthermore, cytotoxic T-cell activity was analyzed in wild-type and TLR9 knockout mice, with/without previous mtDNA administration, followed by injection of an ovalbumin-expressing adenoviral vector. Results Mitochondrial DNA serum concentrations were increased in septic patients (adenosine triphosphatase 6, 123-fold; D-Loop, 76-fold, P < 0.0001) compared with volunteers. Furthermore, a single mtDNA injection caused profound, TLR9-dependent immunosuppression of adaptive T-cell cytotoxicity in wild-type but not in TLR9 knockout mice and evoked various immunosuppressive mechanisms including the destruction of the splenic microstructure, deletion of cross-presenting dendritic cells, and up-regulation of programmed cell death ligand 1 and indoleamine 2,3-dioxygenase. Several of these findings in mice were mirrored in septic patients, and mtDNA concentrations were associated with an increased 30-day mortality. Conclusions The findings of this study imply that mtDNA, an endogenous danger associated molecular pattern, is a hitherto unknown inducer of septic immunoparalysis and one possible link between initial inflammation and subsequent immunosuppression in critically ill patients.