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71.
The reaction of [Ag2(κ2-P,P′-DPEphos)2(μ-OTf)2] (1) (DPEphos = bis(2-(diphenylphosphino)phenyl]ether) with 1,10-phenanthroline (phen) and 4,4′-bipyridine in equimolar ratios afford, respectively, the mononuclear complex [Ag(κ2-P,P′-DPEphos)(phen)][OTf] (2) and the coordination polymer [Ag(κ2-P,P′-DPEphos)(μ-4,4′-bpy)]n[OTf]n (3). In complex 3, the silver atoms are bridged by 4,4′-bipyridine units to form a zigzag metallopolymer. 相似文献
72.
Hari K. Somineni Sini Nagpal Suresh Venkateswaran David J. Cutler David T. Okou Talin Haritunians Claire L. Simpson Ferdouse Begum Lisa W. Datta Antonio J. Quiros Jenifer Seminerio Emebet Mengesha Jonathan S. Alexander Robert N. Baldassano Sharon Dudley-Brown Raymond K. Cross Themistocles Dassopoulos Lee A. Denson Subra Kugathasan 《American journal of human genetics》2021,108(3):431-445
73.
Venkateswaran Subramanian Jessica J. Moorleghen Anju Balakrishnan Deborah A. Howatt Athar H. Chishti Haruhito A. Uchida 《PloS one》2013,8(8)
Background and Objective
Recently, we demonstrated that angiotensin II (AngII)-infusion profoundly increased both aortic protein and activity of calpains, calcium-activated cysteine proteases, in mice. In addition, pharmacological inhibition of calpain attenuated AngII-induced abdominal aortic aneurysm (AA) in mice. Recent studies have shown that AngII infusion into mice leads to aneurysmal formation localized to the ascending aorta. However, the precise functional contribution of calpain isoforms (-1 or -2) in AngII-induced abdominal AA formation is not known. Similarly, a functional role of calpain in AngII-induced ascending AA remains to be defined. Using BDA-410, an inhibitor of calpains, and calpain-1 genetic deficient mice, we examined the relative contribution of calpain isoforms in AngII-induced ascending and abdominal AA development.Methodology/Results
To investigate the relative contribution of calpain-1 and -2 in development of AngII-induced AAs, male LDLr −/− mice that were either calpain-1 +/+ or −/− were fed a saturated fat-enriched diet and infused with AngII (1,000 ng/kg/min) for 4 weeks. Calpain-1 deficiency had no significant effect on body weight or blood pressure during AngII infusion. Moreover, calpain-1 deficiency showed no discernible effects on AngII-induced ascending and abdominal AAs. Interestingly, AngII infusion induced increased expression of calpain-2 protein, thus compensating for total calpain activity in aortas of calpain-1 deficient mice. Oral administration of BDA-410, a calpain inhibitor, along with AngII-infusion significantly attenuated AngII-induced ascending and abdominal AA formation in both calpain-1 +/+ and −/− mice as compared to vehicle administered mice. Furthermore, BDA-410 administration attenuated AngII-induced aortic medial hypertrophy and macrophage accumulation. Western blot and immunostaining analyses revealed BDA-410 administration attenuated AngII-induced C-terminal fragmentation of filamin A, an actin binding cytoskeletal protein in aorta.Conclusion
Calpain-2 compensates for loss of calpain-1, and both calpain isoforms are involved in AngII-induced aortic aneurysm formation in mice. 相似文献74.
A comparison of variable regions within the 16S rRNA gene is widely used to characterize relationships between bacteria and
to identify phylogenetic affiliation of unknown bacteria. In environmental studies, polymerase chain reaction amplification
of 16S rRNA followed by cloning and sequencing of numerous individual clones is an extensively used molecular method for elucidating
microbial diversity. The sequencing process typically utilizes a forward and reverse primer pair to produce two partial reads
(~700 to 800 base pairs each) that overlap and in total cover a large region of the full 16S rRNA sequence (~1.5 k base).
In a typical application, this approach rapidly generates very large numbers of 16S rRNA datasets that can overwhelm manual
processing efforts leading to both delays and errors. In particular, the approach presents two computational challenges: (1)
the assembly of a composite sequence from the two partial reads and (2) the subsequent appropriate identification of the organism
represented by the newly sequenced clones. Herein, we describe a software package, search, trim, identify, track, and capture
the uniqueness of 16S rRNAs using public and in-house database (STITCH), which offers automated sequence pair splicing and
genetic identification, thus simplifying the computationally intensive analysis of large sequencing libraries. The STITCH
software is freely accessible over the Internet at: . 相似文献
75.
Endothelial cell (EC) barrier dysfunction induced by inflammatory agonists is a frequent pathophysiologic event in multiple diseases. The platelet-derived phospholipid sphingosine-1 phosphate (S1P) reverses this dysfunction by potently enhancing the EC barrier through a process involving Rac GTPase-dependent cortical actin rearrangement as an integral step. In this study we explored the role of the ezrin, radixin, and moesin (ERM) family of actin-binding linker protein in modulating S1P-induced human pulmonary EC barrier enhancement. S1P induces ERM translocation to the EC periphery and promotes ERM phosphorylation on a critical threonine residue (Ezrin-567, Radixin-564, Moesin-558). This phosphorylation is dependent on activation of PKC isoforms and Rac1. The majority of ERM phosphorylation on these critical threonine residues after S1P occurs in moesin and ezrin. Baseline radixin phosphorylation is higher than in the other two ERM proteins but does not increase after S1P. S1P-induced moesin and ezrin threonine phosphorylation is not mediated by the barrier enhancing receptor S1PR1 because siRNA downregulation of S1PR1 fails to inhibit these phosphorylation events, while stimulation of EC with the S1PR1-specific agonist SEW2871 fails to induce these phosphorylation events. Silencing of either all ERM proteins or radixin alone (but not moesin alone) reduced S1P-induced Rac1 activation and phosphorylation of the downstream Rac1 effector PAK1. Radixin siRNA alone, or combined siRNA for all three ERM proteins, dramatically attenuates S1P-induced EC barrier enhancement (measured by transendothelial electrical resistance (TER), peripheral accumulation of di-phospho-MLC, and cortical cytoskeletal rearrangement. In contrast, moesin depletion has the opposite effects on these parameters. Ezrin silencing partially attenuates S1P-induced EC barrier enhancement and cytoskeletal changes. Thus, despite structural similarities and reported functional redundancy, the ERM proteins differentially modulate S1P-induced alterations in lung EC cytoskeleton and permeability. These results suggest that ERM activation is an important regulatory event in EC barrier responses to S1P. 相似文献
76.
No?lle Louise O'Regan Svenja Steinfelder Gopinath Venugopal Gopala B. Rao Richard Lucius Aparna Srikantam Susanne Hartmann 《PLoS neglected tropical diseases》2014,8(10)
Background
Monocytes and macrophages contribute to the dysfunction of immune responses in human filariasis. During patent infection monocytes encounter microfilariae in the blood, an event that occurs in asymptomatically infected filariasis patients that are immunologically hyporeactive.Aim
To determine whether blood microfilariae directly act on blood monocytes and in vitro generated macrophages to induce a regulatory phenotype that interferes with innate and adaptive responses.Methodology and principal findings
Monocytes and in vitro generated macrophages from filaria non-endemic normal donors were stimulated in vitro with Brugia malayi microfilarial (Mf) lysate. We could show that monocytes stimulated with Mf lysate develop a defined regulatory phenotype, characterised by expression of the immunoregulatory markers IL-10 and PD-L1. Significantly, this regulatory phenotype was recapitulated in monocytes from Wuchereria bancrofti asymptomatically infected patients but not patients with pathology or endemic normals. Monocytes from non-endemic donors stimulated with Mf lysate directly inhibited CD4+ T cell proliferation and cytokine production (IFN-γ, IL-13 and IL-10). IFN-γ responses were restored by neutralising IL-10 or PD-1. Furthermore, macrophages stimulated with Mf lysate expressed high levels of IL-10 and had suppressed phagocytic abilities. Finally Mf lysate applied during the differentiation of macrophages in vitro interfered with macrophage abilities to respond to subsequent LPS stimulation in a selective manner.Conclusions and significance
Conclusively, our study demonstrates that Mf lysate stimulation of monocytes from healthy donors in vitro induces a regulatory phenotype, characterized by expression of PD-L1 and IL-10. This phenotype is directly reflected in monocytes from filarial patients with asymptomatic infection but not patients with pathology or endemic normals. We suggest that suppression of T cell functions typically seen in lymphatic filariasis is caused by microfilaria-modulated monocytes in an IL-10-dependent manner. Together with suppression of macrophage innate responses, this may contribute to the overall down-regulation of immune responses observed in asymptomatically infected patients. 相似文献77.
Sashidhara KV Palnati GR Avula SR Singh S Jain M Dikshit M 《Bioorganic & medicinal chemistry letters》2012,22(9):3115-3121
A series of novel benzocoumarin amide derivatives have been synthesized and evaluated for their anti-thrombotic activity. Amongst these, compounds 5, 7 and 8 exhibited promising anti-thrombotic profile in an established model of mouse thrombosis. Hence, comprehensive profiling on platelet aggregation and coagulation parameters was carried out to assess its potential as a lead candidate. In vitro treatment of these compounds in mice plasma resulted into significant reduction in ADP (p<0.01) and collagen (p<0.001) induced platelet aggregation. Moreover, Compounds 5, 7 and 8 also significantly increased thrombin time (p<0.05). Thus, in the present study, these benzocoumarin amide derivatives exhibited anti-thrombotic profile via both anti-platelet as well as anti-coagulant action. 相似文献
78.
Ghosh A Sonavane U Andhirka SK Aradhyam GK Joshi R 《Journal of molecular modeling》2012,18(5):2117-2133
Human ocular albinism type 1 protein (OA1)—a member of the G-protein coupled receptor (GPCR) superfamily—is an integral membrane
glycoprotein expressed exclusively by intracellular organelles known as melanocytes, and is responsible for the proper biogenesis
of melanosomes. Mutations in the Oa1 gene are responsible for the disease ocular albinism. Despite its clinical importance, there is a lack of in-depth understanding
of its structure and mechanism of activation due to the absence of a crystal structure. In the present study, homology modeling
was applied to predicting OA1 structure following thorough sequence analysis and secondary structure predictions. The predicted
model had the signature residues and motifs expected of GPCRs, and was used for carrying out molecular docking studies with
an endogenous ligand, l-DOPA and an antagonist, dopamine; the results agreed quite well with the available experimental data. Finally, three sets
of explicit molecular dynamics simulations were carried out in lipid bilayer, the results of which not only confirmed the
stability of the predicted model, but also helped witness some differences in structural features such as rotamer toggle switch,
helical tilts and hydrogen bonding pattern that helped distinguish between the agonist- and antagonist-bound receptor forms.
In place of the typical “D/ERY”-motif-mediated “ionic lock”, a hydrogen bond mediated by the “DAY” motif was observed that
could be used to distinguish the agonist and antagonist bound forms of OA1. In the absence of a crystal structure, this study
helped to shed some light on the structural features of OA1, and its behavior in the presence of an agonist and an antagonist,
which might be helpful in the future drug discovery process for ocular albinism. 相似文献
79.
Subbaiyan GK Waters DL Katiyar SK Sadananda AR Vaddadi S Henry RJ 《Plant biotechnology journal》2012,10(6):623-634
Advances in next-generation sequencing technologies have aided discovery of millions of genome-wide DNA polymorphisms, single nucleotide polymorphisms (SNPs) and insertions-deletions (InDels), which are an invaluable resource for marker-assisted breeding. Whole-genome resequencing of six elite indica rice inbreds (three cytoplasmic male sterile and three restorer lines) resulted in the generation of 338?million 75-bp paired-end reads, which provided 85.4% coverage of the Nipponbare genome. A total of 2?819?086 nonredundant DNA polymorphisms including 2?495?052 SNPs, 160?478 insertions and 163?556 deletions were discovered between the inbreds and Nipponbare, providing an average of 6.8 SNPs/kb across the genome. Distribution of SNPs and InDels in the chromosome was nonrandom with SNP-rich and SNP-poor regions being evident across the genome. A contiguous 4.3-Mb region on chromosome 5 with extremely low SNP density was identified. Overall, 83?262 nonsynonymous SNPs spanning 16?379 genes and 3620 nonsynonymous InDels in 2625 genes have been discovered which provide valuable insights into the basis underlying performance of the inbreds and the hybrids between these inbred combinations. SNPs and InDels discovered from this diverse set of indica rice inbreds not only enrich SNP resources for molecular breeding but also enable the study of genome-wide variations on hybrid performance. 相似文献
80.
Gopala K. Yakala Roel van der Heijden Grietje Molema Martin Schipper Peter Y. Wielinga Robert Kleemann Teake Kooistra Peter Heeringa 《PloS one》2012,7(9)