132 research outputs found
CARBON DIOXIDE SEQUESTRATION: WHEN AND HOWMUCH?
We analyze carbon dioxide (CO sequestration as a strategy to manage future climate change in an optimal economic growth framework. We approach the problem in two ways: first, by using a simple analytical model, and second, by using a numerical optimization model which allows us to explore the problem in a more realistic setting. CO sequestration is not a perfect substitute for avoiding CO2 production because CO2 leaks back to the atmosphere and hence imposes future costs. The āefficiency factorā of CO2 sequestration can be expressed as the ratio of the avoided emissions to the economically equivalent amount of sequestered CO2 emissions. A simple analytical model in terms of a net-present value criterion suggests that short-term sequestration methods such as afforestation can be somewhat ( 60 %) efficient, while long term sequestration (such as deep aquifer or deep ocean sequestration) can be very ( 90%) efficient. A numerical study indicates that CO2 sequestration methods at a cost within the range of present estimates reduce the economically optimal CO2 concentrations and climate related damages. The potential savings associated with CO2 sequestration is equivalent in our utilitarian model to a one-time investment of several percent of present gross world product.
MrgprA3-expressing pruriceptors drive pruritogen-induced alloknesis through mechanosensitive Piezo2 channel
Although touch and itch are coded by distinct neuronal populations, light touch also provokes itch in the presence of exogenous pruritogens, resulting in a phenomenon called alloknesis. However, the cellular and molecular mechanisms underlying the initiation of pruritogen-induced mechanical itch sensitization are poorly understood. Here, we show that intradermal injections of histamine or chloroquine (CQ) provoke alloknesis through activation of TRPV1- and MrgprA3-expressing prurioceptors, and functional ablation of these neurons reverses pruritogen-induced alloknesis. Moreover, genetic ablation of mechanosensitive Piezo2 channel function from MrgprA3-expressing prurioceptors also dampens pruritogen-induced alloknesis. Mechanistically, histamine and CQ sensitize Piezo2 channel function, at least in part, through activation of the phospholipase C (PLC) and protein kinase C-Ī“ (PKCĪ“) signaling. Collectively, our data find a TRPV
Calmodulin Interacts and Regulates Enzyme Activity of the Mammalian Sperm Phospholipase C
Sperm-specific Phospholipase C zeta (PLCĪ¶) is widely considered to be the sole, physiological stimulus responsible for the generation of Ca2+ oscillations that induce egg activation and early embryo development during mammalian fertilization. PLCĪ¶, which is delivered from the fertilizing sperm into the egg cytoplasm, catalyzes the hydrolysis of its membrane-bound phospholipid substrate phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2], triggering the cytoplasmic Ca2+ oscillations through the inositol 1,4,5-trisphosphate (InsP3) signaling pathway. Despite the recent advances the detailed regulatory mechanism of PLCĪ¶ is still unclear, as binding partners of this protein within the sperm or the fertilizing egg have not yet been identified. Calmodulin (CaM) is a ubiquitous Ca2+ sensor in eukaryotic cells. A previous study has reported that CaM directly interacts and regulates the activity of PLC delta 1 protein, a somatic PLC isoform with structural similarities to sperm PLCĪ¶. Bioinformatics analysis revealed putative CaM-binding sites on PLCĪ¶ sequence. In the present study, we have used co-immunoprecipitation analysis and we show that in the presence of Ca2+, human PLCĪ¶ directly interacts with CaM. Isothermal titration calorimetry (ITC) experiments were performed to map the interaction. Three different peptides corresponding to disparate sequences within human PLCĪ¶ were used and it was shown that PLCĪ¶ interacts with CaM via one region of the molecule. In addition, recombinant proteins corresponding to the N- and C-lobe of human CaM were used for ITC experiments, which revealed that CaM interacts with PLCĪ¶ in the presence of Ca2+, only through one of its lobe domains. In vitro PIP2 hydrolysis assays revealed that CaM alters PLCĪ¶ PIP2 hydrolytic activity at high Ca2+ concentrations and, as suggested by liposome binding assays, this appears to be due to CaM binding to PLCĪ¶ affecting proper access of the enzyme active site to its substrate PI(4,5)P2
A TRPV4-dependent neuroimmune axis in the spinal cord promotes neuropathic pain
Microglia, resident macrophages of the CNS, are essential to brain development, homeostasis, and disease. Microglial activation and proliferation are hallmarks of many CNS diseases, including neuropathic pain. However, molecular mechanisms that govern the spinal neuroimmune axis in the setting of neuropathic pain remain incompletely understood. Here, we show that genetic ablation or pharmacological blockade of transient receptor potential vanilloid type 4 (TRPV4) markedly attenuated neuropathic pain-like behaviors in a mouse model of spared nerve injury. Mechanistically, microglia-expressed TRPV4 mediated microglial activation and proliferation and promoted functional and structural plasticity of excitatory spinal neurons through release of lipocalin-2. Our results suggest that microglial TRPV4 channels reside at the center of the neuroimmune axis in the spinal cord, which transforms peripheral nerve injury into central sensitization and neuropathic pain, thereby identifying TRPV4 as a potential new target for the treatment of chronic pain
Neutron scattering studies of heterogeneous catalysis
Understanding the structural dynamics/evolution of catalysts and the related surface chemistry is essential for establishing structureācatalysis relationships, where spectroscopic and scattering tools play a crucial role. Among many such tools, neutron scattering, though less-known, has a unique power for investigating catalytic phenomena. Since neutrons interact with the nuclei of matter, the neutronānucleon interaction provides unique information on light elements (mainly hydrogen), neighboring elements, and isotopes, which are complementary to X-ray and photon-based techniques. Neutron vibrational spectroscopy has been the most utilized neutron scattering approach for heterogeneous catalysis research by providing chemical information on surface/bulk species (mostly H-containing) and reaction chemistry. Neutron diffraction and quasielastic neutron scattering can also supply important information on catalyst structures and dynamics of surface species. Other neutron approaches, such as small angle neutron scattering and neutron imaging, have been much less used but still give distinctive catalytic information. This review provides a comprehensive overview of recent advances in neutron scattering investigations of heterogeneous catalysis, focusing on surface adsorbates, reaction mechanisms, and catalyst structural changes revealed by neutron spectroscopy, diffraction, quasielastic neutron scattering, and other neutron techniques. Perspectives are also provided on the challenges and future opportunities in neutron scattering studies of heterogeneous catalysis
Parvovirus B19 infection in Tunisian patients with sickle-cell anemia and acute erythroblastopenia
<p>Abstract</p> <p>Background</p> <p>Human parvovirus B19 is the etiologic agent of erythema infectiosum in children. It is also associated with other clinical manifestations in different target groups. Patients with chronic hemolytic anemia are at high risk of developing acute erythroblastopenia following infection by the virus. They usually become highly viremic and pose an increased risk of virus transmission. Close monitoring of such high risk groups is required for epidemiologic surveillance and disease prevention activities. Here we report a molecular epidemiological study on B19 virus infection in Tunisian patients with chronic hemolytic anemia.</p> <p>Methods</p> <p>This study was conducted on 92 young chronic hemolytic anemia patients who attended the same ward at the National Bone Marrow Transplantation Center of Tunis and 46 controls from a different hospital. Screening for IgM and IgG anti-B19 antibodies was performed using commercially available enzyme immunoassays and B19 DNA was detected by nested PCR in the overlapping <it>VP1/VP2 </it>region. DNA was sequenced using dideoxy-terminator cycle sequencing technology.</p> <p>Results</p> <p>Anti-parvovirus B19 IgG antibodies were detected in 26 of 46 sickle-cell anemia patients, 18 of 46 Ī²-thalassemia and 7 of 46 controls. Anti-parvovirus B19 IgM antibodies were detected only in 4 of the sickle-cell anemia patients: two siblings and two unrelated who presented with acute erythroblastopenia at the time of blood collection for this study and had no history of past transfusion. B19 DNA was detected only in sera of these four patients and the corresponding 288 bp nested DNA amplicons were sequenced. The sequences obtained were all identical and phylogenetic analysis showed that they belonged to a new B19 virus strain of Genotype1.</p> <p>Conclusion</p> <p>A new parvovirus B19 strain of genotype1 was detected in four Tunisian patients with sickle-cell anemia. Virus transmission appeared to be nosocomial and resulted in acute erythroblastopenia in the four patients. The possibility of independent transmission of this B19 variant to the patients is unlikely in light of the present epidemiological data. However this possibility cannot be ruled out because of the low genetic variability of the virus.</p
Prevalence and Determinants of Metabolic Syndrome among Women in Chinese Rural Areas
BACKGROUND AND AIMS: Metabolic syndrome (MS) is prevalent in recent years but few data is reported in the rural areas in China. The aim of this study was to examine MS prevalence and its risk factors among women in rural China. METHODS AND RESULTS: The Nantong Metabolic Syndrome Study (NMSS), a population based cross-sectional study, was conducted during 2007-2008 in Nantong, China. In person interviews, blood glucose and lipid measurements were completed for 13,505 female participants aged 18-74 years. The International Diabetes Federation (IDF), the US Third Report of the National Cholesterol Education Program, the Adult Treatment Panel (ATPIII) and modified ATPIII for Asian population has determined three criteria of MS. These criteria for MS were used and compared in this study. The prevalence of MS was 22.0%, 16.9% and 23.3% according to IDF, ATPIII and ATPIII-modified criteria, respectively. Levels of agreement of these criteria for MS were above 0.75. We found that vigorous-intensity of occupational physical activity was associated with a low prevalence of MS with OR of 0.76 (95% confidence interval (CI): 0.63-0.91). Rice wine drinkers (alcohol >12.8 g/day) had about 34% low risks of developing MS with OR of 0.66 (95% CI: 0.48-0.91), compared with non-drinkers. Odds ratio of MS was 1.81 (95% CI: 1.15-2.84) in women who smoked more than 20 pack-years, compared to non-smokers. Odds ratio of MS was 1.56 (95% CI: 1.25-1.95) in women who had familial history of diseases, including hypertension, diabetes and stroke, compared to women without familial history of those diseases. CONCLUSION: MS is highly prevalent among women in rural China. Both physical activity and rice wine consumption play a protective role, while family history and smoking are risk factors in MS development. Educational programs should be established for promoting healthy lifestyles and appropriate interventions in rural China
The Concise Guide to PHARMACOLOGY 2023/24:Introduction and Other Protein Targets
The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.16176. In addition to this overview, in which are identified 'Other protein targets' which fall outside of the subsequent categorisation, there are six areas of focus: G protein-coupled receptors, ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.</p
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