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1 PAM 11 was very active in feeding inhibition in rodents,
2 PAM acts as an allosteric effector and triggers the inte
3 PAM neurons show increased activity following caffeine a
4 PAM sequences are known to vary considerably between sys
5 PAM-1 lacking both glycosylation sites (PAM-1/OSX; where
6 PAM-ABP and siRNA formed polyplexes with average diamete
7 PAM-SCANR and the PAM wheel identified known functional
8 PAMs and NAMs of mGluRs, either of which can inhibit evo
9 PAMs from pigs that possessed the hCD163L1 domain 8 homo
12 e found that FnCas9 recognizes the 5'-NGG-3' PAM, and used the structural information to create a var
13 s to edit endogenous sites with the 5'-YG-3' PAM, thus expanding the target space of the CRISPR-Cas9
17 yl)isoxazole (CMPI) has been identified as a PAM selective for neuronal nAChRs containing thealpha4 s
21 ombined properties of agonists and PAMs (ago-PAM) and produce very effective channel activation (dire
22 that Cas proteins can be engineered to alter PAM recognition, opening new opportunities to develop CR
24 resolution structures delineated the altered PAM recognition mechanisms of the AsCpf1 variants, provi
28 ound that nucleotides at both PAM-distal and PAM-proximal regions of the sgRNA are significantly corr
29 t displayed both high intrinsic efficacy and PAM activity, those that showed no detectable agonism bu
31 ive allosteric modulators (an mGluR5 NAM and PAM) for TSC, using a mutant mouse model with neuronal l
32 s all wavelengths (Flambda , 670-850 nm) and PAM fluorescence parameters under a range of actinic lig
33 for association with pregnancy outcomes and PAM indicators using linear and logistic multivariate mo
34 talytic function, guide RNA specificity, and PAM requirements and reducing off-target activity for th
35 have the combined properties of agonists and PAMs (ago-PAM) and produce very effective channel activa
37 findings indicate that free DNA termini and PAMs are conserved features important for CRISPR spacer
39 9 specificity wherein gRNA-DNA mismatches at PAM-distal bases modulate different biophysical paramete
41 first small molecule modulator to attenuate PAM complex activity, likely through binding to the C-te
43 g frames, that are identical (or have BLOSUM/PAM similarity that exceeds a user-specified value) to t
45 phy (NIR-VISPAOCT) system that combines both PAM and OCT with a conventional surgical microscope.
46 ate that AcrIIA4 competitively occupies both PAM-interacting and non-target DNA strand cleavage catal
49 d high molecular weight complexes containing PAM-1; the ability of PAM-1/OSX to form similar complexe
55 iew, we discuss the properties of the CRISPR PAM and the emerging tools for determining, visualizing,
66 says to show that BMS-986187 is an effective PAM at the mu-OR and at the kappa-opioid receptor (kappa
68 NA binding to PAM favors separation of a few PAM-proximal protospacer base pairs allowing initial tar
69 ally targets critical residues essential for PAM duplex recognition, as well as blocks target DNA acc
72 d DNA beyond a short threshold distance from PAM into the Cas9/single-guide RNA (sgRNA) interior is h
74 NOT-gate repression) to elucidate functional PAMs as well as an interactive visualization scheme term
75 nd the PAM wheel identified known functional PAMs while revealing complex sequence-activity landscape
76 We identify a large number of functional PAMs that can promote interference, priming or both acti
77 ns of elucidating and visualizing functional PAMs toward accelerating our ability to understand and e
79 f NMDARs and AMPA receptors (AMPARs), GluN2A PAMs with good selectivity against AMPARs were identifie
81 for cleavage, it is unknown whether and how PAM binding activates Cas9 for DNA cleavage at spatially
82 supports the interest of a serotonin 5-HT2CR PAM as a promising therapeutic approach for obesity.
83 FI-FH proteolytically cleaves C3b into iC3b, PAM-bound hPm catalyzes cleavage of iC3b into multiple s
85 , these studies show that we have identified PAMs of the D2 and D3 receptors both in vitro and in viv
89 Cas9 tolerance to single-base mismatches in PAM-distal region than to PAM-proximal region and the hi
91 from recent studies of systemically injected PAMs and NAMs of mGluRs in rodents and monkeys, focusing
96 ivity at a wide variety of receptors, lacked PAM activity at related Gi-coupled G protein-coupled rec
99 n, we describe the characterization of an M1 PAM radioligand, 8-((1S,2S)-2-hydroxycyclohexyl)-5-((6-(
100 is a strong positive correlation between M1 PAM binding affinity and functional activity, and that [
102 en affinity values generated for nineteen M1 PAMs in the [(3)H]PT-1284 binding assay and the EC50 val
104 se model and support a role for selective M1 PAMs as a novel approach for the treatment of schizophre
105 pocampal muscarinic signaling using M1 mAChR PAMs restored memory loss and slowed the progression of
108 ere compared to porcine alveolar macrophage (PAM) in terms of surface marker phenotype, susceptibilit
109 stablished the porcine alveolar macrophages (PAM) cells model co-infected with PRRSV/PCV2 with modifi
111 ctions between porcine alveolar macrophages (PAMs) and wild-type A. pleuropneumoniae (5b WT) or an Ad
112 phenotyping of porcine alveolar macrophages (PAMs) showed that pigs with the KO or SRCR domain 5 dele
116 ster of neurons, the paired anterior medial (PAM) cluster of dopaminergic neurons, as the ones releva
119 disease primary amoebic meningoencephalitis (PAM) and can be found in drinking water systems in many
120 ection, primary amoebic meningoencephalitis (PAM) induced by Naegleria fowleri is extremely lethal, w
121 riven selection would have resulted in mGlu2 PAMs with high values for kon but not necessarily optimi
123 ach used in its development, our novel mGlu5 PAM improves RS phenotypes and synaptic plasticity defec
124 trophysiology to determine whether the mGlu5 PAM VU0409551 directly enhances NMDAR function in hippoc
125 pport for the continued development of mGlu5 PAMs as potential therapeutic agents for use in RS, and,
126 mproved solubility compared with other mGlu5 PAMs, thus allowing brain-site-specific pharmacological
127 monkey using a structurally distinct mGluR2 PAM ligand with affinity for the same site, demonstratin
129 nt fast functional photoacoustic microscopy (PAM) for three-dimensional high-resolution, high-speed i
130 omography (OCT) or photoacoustic microscopy (PAM) has been independently combined with conventional s
133 cage 1 undergoes post-assembly modification (PAM) via a Diels-Alder cycloaddition of the anthracene p
134 ultaneously with pulse-amplitude modulation (PAM) and spectrally resolved fluorescence over the same
135 The novel positive allosteric modulator (PAM) 1-(4-(2,4-difluorophenyl) piperazin-1-yl)-2-((4-flu
138 ignaling with positive allosteric modulator (PAM) blocked aberrant LTP in dSPNs, enabled LTP reversal
139 ype-selective positive allosteric modulator (PAM) contributes to the gastrointestinal (GI) and cardio
140 of M1 with a positive allosteric modulator (PAM) has emerged as a new approach to achieve selective
141 (mAChR) via a positive allosteric modulator (PAM) is a new approach for the treatment of the cognitiv
142 esting that a positive allosteric modulator (PAM) of alpha7 receptors, JNJ-39393406, may aid smoking
143 shown to be a positive allosteric modulator (PAM) of GABA currents with alpha1beta2gamma2, alpha1beta
145 hat acts as a positive allosteric modulator (PAM) of the rat and human dopamine D2 and D3 receptors.
146 ective mGluR4 positive allosteric modulator (PAM) with good water solubility and demonstrating consis
147 ffects of the positive allosteric modulator (PAM), ML380, and negative allosteric modulator, ML375.
149 a novel mGlu5 positive allosteric modulator (PAM), termed VU0462807, can rescue synaptic plasticity d
150 lly active M1 positive allosteric modulator (PAM), VU0453595, allowed us to evaluate the impact of se
153 a series of positive allosteric modulators (PAMs) acting on the human alpha7 nicotinic acetylcholine
154 velopment of positive allosteric modulators (PAMs) and negative allosteric modulators (NAMs) of mGluR
155 or 5 (mGlu5)-positive allosteric modulators (PAMs) are currently being developed to treat cognitive d
160 e identified positive allosteric modulators (PAMs) of NMDARs with selectivity for GluN2A subunit-cont
162 A number of positive allosteric modulators (PAMs) that enhance GABA's actions on neuronal GABAA-Rs a
163 to selective positive allosteric modulators (PAMs), which increase the efficiency of channel activati
164 NARW movements, passive acoustic monitoring (PAM) was used in this study in order to better capture y
165 ptidylglycine alpha-amidating monooxygenase (PAM) (EC 1.14.17.3) catalyzes peptide amidation, a cruci
166 ptidylglycine alpha-amidating monooxygenase (PAM), an enzyme required for generating amidated bioacti
167 and flanked by a protospacer adjacent motif (PAM) and is widely used for genome editing in various or
168 sence of a short protospacer adjacent motif (PAM) flanking the target site, and subsequent R-loop for
170 avage requires a protospacer adjacent motif (PAM) juxtaposed with the DNA target sequence, thus const
172 s in the seed or protospacer adjacent motif (PAM) of the target sequence cause immune failure and all
174 s with different protospacer-adjacent motif (PAM) specificities to expand the number of sites that ca
176 rches gRNA by 3' protospacer-adjacent motif (PAM), and possible off-targets, and scores the conservat
177 ches proximal to protospacer-adjacent motif (PAM), demonstrating that mismatches encountered early du
179 sequences as the protospacer adjacent motif (PAM), thereby expanding the target range of Cpf1-mediate
180 trategy based on Protospacer Adjacent Motif (PAM)-altering SNPs to target patient-specific CRISPR/Cas
190 ng property of pectinated atrial myocardium (PAM) and the ventricular conduction system (VCS) and is
191 support further testing of this alpha7 nAChR PAM compound for possible efficacy in smoking cessation,
192 , an engineered Cas9-VQR variant with 5'-NGA PAM specificities is used to induce base conversion in z
194 t complexes containing PAM-1; the ability of PAM-1/OSX to form similar complexes was markedly diminis
195 demonstrates that a large-scale analysis of PAM data provides significant value to understanding and
196 e for controlled endoproteolytic cleavage of PAM and the separation of soluble peptidylglycine alpha-
198 t evidence of radical-induced degradation of PAM under HPT hydraulic fracturing conditions without ad
199 tly it catalyzed the chemical degradation of PAM, likely due to dissolution of Fe(2+) at low pH.
200 soluble fragment of the cytosolic domain of PAM-1 was produced in the endocytic pathway and entered
201 ansfection efficiency and VEGF expression of PAM-ABP using gWiz-Luc and pbeta-VEGF were higher than t
202 o-immunoprecipitation of a small fraction of PAM and Atp7a supports the suggestion that copper can be
203 SX; where OSX is O-glycan-depleted mutant of PAM-1) was stably expressed in AtT-20 corticotrope tumor
204 riginal cage, demonstrating the potential of PAM for tuning the binding properties of supramolecular
212 Consensus docking with an extended series of PAMs with chemical similarity to A-867744, TBS-516, and
213 RISPR/Cas9 guide RNAs (gRNAs) that depend on PAM sites generated by SNP alleles on the mutant chromos
215 onstrate that, contrary to many reports, one PAM-proximal mismatch is insufficient to abolish dCas9-m
219 ion coefficients of Pu(V) in polyacrylamide (PAM) gel in the presence of humic acid using a diffusion
224 , we show that clinically applicable GABAA-R PAMs can increase significantly INS-1 ss-cell replicatio
226 of this endogenous hormone-like CB2 receptor PAM, with unforeseen opposite allosteric effects on cann
227 reatments were the alpha7 nicotinic receptor PAM JNJ-39393406 (100 mg b.i.d.) or placebo (double-blin
228 m) directly via an hPg/hPm surface receptor (PAM), we show that both FI-FH and hPm sequentially cleav
230 ype III-A CRISPR-Cas system does not require PAM or seed sequences, and thus prevents viral escape vi
231 that showed no detectable agonism but robust PAM activity and ligands that displayed robust allosteri
233 sitive, and tunable screen termed PAM-SCANR (PAM screen achieved by NOT-gate repression) to elucidate
234 is way, both microscopic and cross-sectional PAM and OCT images are concurrently displayed on the ocu
235 ctor, it can back-project 2D cross-sectional PAM and OCT images onto the microscopic view plane.
237 (PF-06767832) is a high quality M1 selective PAM that has well-aligned physicochemical properties, go
239 udies have focused on three alpha7-selective PAMs (A-867744, TBS-516, and TQS) that display similar e
240 ite and characterization of GluN2A-selective PAMs provide powerful molecular tools to dissect NMDAR f
242 which is flanked by single guide RNA (sgRNA)-PAM sequences and is released after CRISPR/Cas9 cleavage
243 GABAA receptors, while having no significant PAM effect on alphabeta receptors or alpha1beta1gamma2,
245 o realize motionless volumetric imaging, SIR-PAM combines two-dimensional Fourier-spectrum optical ex
247 PAM-1 lacking both glycosylation sites (PAM-1/OSX; where OSX is O-glycan-depleted mutant of PAM-
251 R/K548V/N552R, which recognize TYCV and TATV PAMs, respectively, with enhanced activities in vitro an
252 odulated chlorophyll fluorescence technique (PAM) allows quantitative leaf level monitoring of the ut
253 in vivo, positive, and tunable screen termed PAM-SCANR (PAM screen achieved by NOT-gate repression) t
263 is study also supports a direct role for the PAM complex in the import of substrates that are lateral
264 % inhibitory concentration = 9.6 nM) for the PAM site of mGluR2, was evaluated as a selective mGluR2
265 uplex DNA binding promote DNA bending in the PAM-proximal region during early steps of Cas9/guide RNA
270 d 25 bp upstream and 40 bp downstream of the PAM site, while 20-30 bp of the binding site itself are
271 y analyses, the peak molecular weight of the PAM was reduced by 2 orders of magnitude, from roughly 1
272 advance our mechanistic understanding of the PAM-dependent, crRNA-guided DNA cleavage by the Cpf1 fam
273 e structures revealed that, depending on the PAM sequences, LbCpf1 undergoes conformational changes t
274 so propose a standard means of orienting the PAM to simplify how its location and sequence are commun
275 RVR and RR variants primarily recognize the PAM-complementary nucleotides via the substituted residu
276 enomic site as well as those surrounding the PAM region are a major component of the prediction capab
277 interactive visualization scheme termed the PAM wheel to convey individual PAM sequences and their a
278 e the structural basis for understanding the PAM-dependent directional R-loop formation process.
279 hanges to form altered interactions with the PAM-containing DNA duplexes, thereby achieving the relax
282 ound that Adh was shown to interact with the PAMs membrane protein OR5M11, an olfactory receptor, res
286 er can be transferred directly from Atp7a to PAM, a process that can occur only when both proteins ar
287 results show that Cas9/guide RNA binding to PAM favors separation of a few PAM-proximal protospacer
289 base mismatches in PAM-distal region than to PAM-proximal region and the high specificity and efficie
291 Whereas wild-type AsCpf1 recognizes the TTTV PAM, the RVR (S542R/K548V/N552R) and RR (S542R/K607R) va
293 lized PAM-1/OSX was rapidly degraded; unlike PAM-1, very little internalized PAM-1/OSX was detected i
296 circulation in the eye by combining in vivo PAM imaging and an ocular surface estimation method base
297 hemical degradation of high molecular weight PAM, including the effects of shale, oxygen, temperature
299 lso review results from rat studies in which PAMs or NAMs of mGluRs were injected intracranially to r
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