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81.
82.
Stewart AK Shmukler BE Vandorpe DH Reimold F Heneghan JF Nakakuki M Akhavein A Ko S Ishiguro H Alper SL 《American journal of physiology. Cell physiology》2011,301(2):C289-C303
The secretin-stimulated human pancreatic duct secretes HCO(3)(-)-rich fluid essential for normal digestion. Optimal stimulation of pancreatic HCO(3)(-) secretion likely requires coupled activities of the cystic fibrosis transmembrane regulator (CFTR) anion channel and apical SLC26 Cl(-)/HCO(3)(-) exchangers. However, whereas stimulated human and guinea pig pancreatic ducts secrete ~140 mM HCO(3)(-) or more, mouse and rat ducts secrete ~40-70 mM HCO(3)(-). Moreover, the axial distribution and physiological roles of SLC26 anion exchangers in pancreatic duct secretory processes remain controversial and may vary among mammalian species. Thus the property of high HCO(3)(-) secretion shared by human and guinea pig pancreatic ducts prompted us to clone from guinea pig pancreatic duct cDNAs encoding Slc26a3, Slc26a6, and Slc26a11 polypeptides. We then functionally characterized these anion transporters in Xenopus oocytes and human embryonic kidney (HEK) 293 cells. In Xenopus oocytes, gpSlc26a3 mediated only Cl(-)/Cl(-) exchange and electroneutral Cl(-)/HCO(3)(-) exchange. gpSlc26a6 in Xenopus oocytes mediated Cl(-)/Cl(-) exchange and bidirectional exchange of Cl(-) for oxalate and sulfate, but Cl(-)/HCO(3)(-) exchange was detected only in HEK 293 cells. gpSlc26a11 in Xenopus oocytes exhibited pH-dependent Cl(-), oxalate, and sulfate transport but no detectable Cl(-)/HCO(3)(-) exchange. The three gpSlc26 anion transporters exhibited distinct pharmacological profiles of (36)Cl(-) influx, including partial sensitivity to CFTR inhibitors Inh-172 and GlyH101, but only Slc26a11 was inhibited by PPQ-102. This first molecular and functional assessment of recombinant SLC26 anion transporters from guinea pig pancreatic duct enhances our understanding of pancreatic HCO(3)(-) secretion in species that share a high HCO(3)(-) secretory output. 相似文献
83.
Inherited Interleukin-12 Deficiency: IL12B Genotype and Clinical Phenotype of 13 Patients from Six Kindreds 总被引:12,自引:0,他引:12 下载免费PDF全文
Capucine Picard Claire Fieschi Frédéric Altare Suliman Al-Jumaah Sami Al-Hajjar Jacqueline Feinberg Stéphanie Dupuis Claire Soudais Ibrahim Zaid Al-Mohsen Emmanuelle Génin David Lammas Dinakantha S. Kumararatne Tony Leclerc Arash Rafii Husn Frayha Belinda Murugasu Lee Bee Wah Raja Sinniah Michael Loubser Emi Okamoto Abdulaziz Al-Ghonaium Haysam Tufenkeji Laurent Abel Jean-Laurent Casanova 《American journal of human genetics》2002,70(2):336-348
Interleukin-12 (IL12) is a cytokine that is secreted by activated phagocytes and dendritic cells and that induces interferon-gamma production by natural-killer and T lymphocytes. It consists of two subunits, p35 and p40, which are encoded by IL12A and IL12B, respectively. The first reported patient with a genetic cytokine disorder was a Pakistani child, who was homozygous for a large loss-of-function deletion (g.482+82_856-854del) in IL12B. This IL12-deficient child suffered from infections caused by bacille Calmette-Guérin (BCG) and Salmonella enteritidis. We herein report 12 additional patients from five other kindreds. In one kindred from India, the same large deletion that was described elsewhere (g.482+82_856-854del) was identified. In four kindreds from Saudi Arabia, a recessive loss-of-function frameshift insertion (g.315_316insA) was found. A conserved haplotype encompassing the IL12B gene suggested that a founder effect accounted for the recurrence of each mutation. The two founder mutational events-g.482+82_856-854del and g.315_316insA-were estimated to have occurred approximately 700 and approximately 1,100 years ago, respectively. Among a total of 13 patients with IL12 deficiency, 1 child had salmonellosis only and 12 suffered from clinical disease due to BCG or environmental nontuberculous mycobacteria. One patient also had clinical disease caused by virulent Mycobacterium tuberculosis, five patients had clinical disease caused by Salmonella serotypes, and one patient had clinical disease caused by Nocardia asteroides. The clinical outcome varies from case to case, since five patients (aged 2-11 years) died of overwhelming infection, whereas eight patients (aged 3-12 years) are still in good health and are not currently taking antibiotics. In conclusion, IL12 deficiency is not limited to a single kindred, shows significant variability of outcome, and should be considered in the genetic diagnosis of patients with mycobacteriosis and/or salmonellosis. To date, two founder IL12B mutations have been identified, accounting for the recurrence of a large deletion and a small insertion within populations from the Indian subcontinent and from the Arabian Peninsula, respectively. 相似文献
84.
Reza Abbasifar Andrew M. Kropinski Parviz M. Sabour Hans-Wolfgang Ackermann Argentina Alanis Villa Arash Abbasifar Mansel W. Griffiths 《Journal of virology》2012,86(24):13830-13831
Cronobacter sakazakii is a pathogen that predominantly infects immunocompromised individuals, especially infants, where it causes meningitis. The genome of lytic C. sakazakii myovirus vB_CsaM_GAP31 has been fully sequenced. It consists of 147,940 bp and has a G+C content of 46.3%. A total of 295 genes, including 269 open reading frames and 26 tRNA genes, were identified. This phage is related to Salmonella phage PVP-SE1 and coliphages vB_EcoM-FV3 and rV5. 相似文献
85.
Hadipour-Niktarash A 《Journal of computational neuroscience》2006,20(3):299-320
In Parkinson’s disease, neurons of the internal segment of the globus pallidus (GPi) display the low-frequency tremor-related
oscillations. These oscillatory activities are transmitted to the thalamic relay nuclei. Computer models of the interacting
thalamocortical (TC) and thalamic reticular (RE) neurons were used to explore how the TC-RE network processes the low-frequency
oscillations of the GPi neurons. The simulation results show that, by an interaction between the TC and RE neurons, the TC-RE
network transforms a low-frequency oscillatory activity of the GPi neurons to a higher frequency of oscillatory activity of
the TC neurons (the superharmonic frequency transformation). In addition to the interaction between the TC and RE neurons,
the low-threshold calcium current in the RE and TC neurons and the hyperpolarization-activated cation current (I h) in the TC neurons have significant roles in the superharmonic frequency transformation property of the TC-RE network. The
external globus pallidus (GPe) oscillatory activity, which is directly transmitted to the RE nucleus also displays a significant
modulatory effect on the superharmonic frequency transformation property of the TC-RE network.
Action Editor: John Rinzel 相似文献
86.
Myocardial fiber orientation is a topic that has recently received much attention in connection with cardiac pumping function.
The twisting motion of the cardiac base to apex can be a direct result of this geometric orientation of these fibers. One
important question that has not been addressed yet is whether there is any relationship between the contractile energy expenditure
and the geometric orientation of myocardial fibers. In the present work, we study the effect of contractile fiber orientation
on pumping function. We particularly compare the effect of fiber geometry on ejection fraction, and on the energy required
for contraction in both cylindrical and half-ellipsoid shell models. The analytical models we used signify the importance
of twisting motion in minimizing the energy required to generate certain ejection fraction. Indeed, we quantified that if
the angle of contractile fibers is appropriate for the shape and the size of the pump, twisting scheme can tremendously reduce
the energy requirement for pumping. 相似文献
87.
Topp S Reynoso CM Seeliger JC Goldlust IS Desai SK Murat D Shen A Puri AW Komeili A Bertozzi CR Scott JR Gallivan JP 《Applied and environmental microbiology》2010,76(23):7881-7884
We developed a series of ligand-inducible riboswitches that control gene expression in diverse species of Gram-negative and Gram-positive bacteria, including human pathogens that have few or no previously reported inducible expression systems. We anticipate that these riboswitches will be useful tools for genetic studies in a wide range of bacteria. 相似文献
88.
89.
Amir Bahmani Kyle Ferriter Vandhana Krishnan Arash Alavi Amir Alavi Philip S. Tsao Michael P. Snyder Cuiping Pan 《PLoS computational biology》2021,17(5)
Genomic data analysis across multiple cloud platforms is an ongoing challenge, especially when large amounts of data are involved. Here, we present Swarm, a framework for federated computation that promotes minimal data motion and facilitates crosstalk between genomic datasets stored on various cloud platforms. We demonstrate its utility via common inquiries of genomic variants across BigQuery in the Google Cloud Platform (GCP), Athena in the Amazon Web Services (AWS), Apache Presto and MySQL. Compared to single-cloud platforms, the Swarm framework significantly reduced computational costs, run-time delays and risks of security breach and privacy violation. 相似文献
90.
Nasser Hashemi Goradel Nasir Mohajel Ziba Veisi Malekshahi Samira Jahangiri Masoud Najafi Bagher Farhood Keywan Mortezaee Babak Negahdari Arash Arashkia 《Journal of cellular physiology》2019,234(6):8636-8646
Cancer therapy using oncolytic viruses is an emerging area, in which viruses are engineered to selectively propagate in tumor tissues without affecting healthy cells. Because of the advantages that adenoviruses (Ads) have over other viruses, they are more considered. To achieve tumor selectivity, two main modifications on Ads genome have been applied: small deletions and insertion of tissue- or tumor-specific promoters. Despite oncolytic adenoviruses ability in tumor cell lysis and immune responses stimulation, to further increase their antitumor effects, genomic modifications have been carried out including insertion of checkpoint inhibitors and antigenic or immunostimulatory molecules into the adenovirus genome and combination with dendritic cells and chemotherapeutic agents. This study reviews oncolytic adenoviruses structures, their antitumor efficacy in combination with other therapeutic strategies, and finally challenges around this treatment approach. 相似文献