Membrane organization in G‐protein mechanisms

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154346/1/fsb2008012006.pd

He Said, She Said: Style Transfer for Shifting the Perspective of Dialogues

In this work, we define a new style transfer task: perspective shift, which reframes a dialogue from informal first person to a formal third person rephrasing of the text. This task requires challenging coreference resolution, emotion attribution, and interpretation of informal text. We explore several baseline approaches and discuss further directions on this task when applied to short dialogues. As a sample application, we demonstrate that applying perspective shifting to a dialogue summarization dataset (SAMSum) substantially improves the zero-shot performance of extractive news summarization models on this data. Additionally, supervised extractive models perform better when trained on perspective shifted data than on the original dialogues. We release our code publicly.Comment: Findings of EMNLP 2022, 18 page

G protein-coupled estrogen receptor (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

The G protein-coupled estrogen receptor (GPER, nomenclature as agreed by the NC-IUPHAR Subcommittee on the G protein-coupled estrogen receptor [24]) was identified following observations of estrogen-evoked cyclic AMP signalling in breast cancer cells [2], which mirrored the differential expression of an orphan 7-transmembrane receptor GPR30 [5]. There are observations of both cell-surface and intracellular expression of the GPER receptor [27, 32]. Selective agonist/ antagonists for GPER have been characterized [24]. Antagonists of the nuclear estrogen receptor, such as fulvestrant [10], tamoxifen [27, 32] and raloxifene [23], as well as the flavonoid 'phytoestrogens' genistein and quercetin [16], are agonists of GPER. A complete review of GPER pharmacology has been recently published [24]. The roles of GPER in physiological systems throughout the body (cardiovascular, metabolic, endocrine, immune, reproductive) and in cancer have also been reviewed [24, 25, 18, 15, 8]

ChatGPT MT: Competitive for High- (but not Low-) Resource Languages

Large language models (LLMs) implicitly learn to perform a range of language tasks, including machine translation (MT). Previous studies explore aspects of LLMs' MT capabilities. However, there exist a wide variety of languages for which recent LLM MT performance has never before been evaluated. Without published experimental evidence on the matter, it is difficult for speakers of the world's diverse languages to know how and whether they can use LLMs for their languages. We present the first experimental evidence for an expansive set of 204 languages, along with MT cost analysis, using the FLORES-200 benchmark. Trends reveal that GPT models approach or exceed traditional MT model performance for some high-resource languages (HRLs) but consistently lag for low-resource languages (LRLs), under-performing traditional MT for 84.1% of languages we covered. Our analysis reveals that a language's resource level is the most important feature in determining ChatGPT's relative ability to translate it, and suggests that ChatGPT is especially disadvantaged for LRLs and African languages.Comment: 27 pages, 9 figures, 14 table

G protein-coupled estrogen receptor in GtoPdb v.2021.3

The G protein-coupled estrogen receptor (GPER, nomenclature as agreed by the NC-IUPHAR Subcommittee on the G protein-coupled estrogen receptor [25]) was identified following observations of estrogen-evoked cyclic AMP signalling in breast cancer cells [2], which mirrored the differential expression of an orphan 7-transmembrane receptor GPR30 [6]. There are observations of both cell-surface and intracellular expression of the GPER receptor [28, 33]. Selective agonist/ antagonists for GPER have been characterized [25]. Antagonists of the nuclear estrogen receptor, such as fulvestrant [11], tamoxifen [28, 33] and raloxifene [24], as well as the flavonoid 'phytoestrogens' genistein and quercetin [17], are agonists of GPER. A complete review of GPER pharmacology has been published [25]. The roles of GPER in physiological systems throughout the body (cardiovascular, metabolic, endocrine, immune, reproductive) and in cancer have also been reviewed [25, 26, 19, 16, 9]. The GPER-selective agonist G-1 is currently in Phase I/II clinical trials for cancer (NCT04130516)

Unlimiformer: Long-Range Transformers with Unlimited Length Input

Since the proposal of transformers, these models have been limited to bounded input lengths, because of their need to attend to every token in the input. In this work, we propose Unlimiformer: a general approach that wraps any existing pretrained encoder-decoder transformer, and offloads the cross-attention computation to a single k-nearest-neighbor (kNN) index, while the returned kNN distances are the attention dot-product scores. This kNN index can be kept on either the GPU or CPU memory and queried in sub-linear time; this way, we can index practically unlimited input sequences, while every attention head in every decoder layer retrieves its top-k keys, instead of attending to every key. We evaluate Unlimiformer on several long-document and book-summarization benchmarks, showing that it can process even 500k token-long inputs from the BookSum dataset, without any input truncation at test time. We demonstrate that Unlimiformer improves pretrained models such as BART and Longformer by extending them to unlimited inputs without additional learned weights and without modifying their code. We make our code and models publicly available at https://github.com/abertsch72/unlimiformer .Comment: NeurIPS 202

Large-scale purification of [alpha]2-adrenergic receptor-enriched membranes from human platelets. Persistent association of guanine nucleotides with nonpurified membranes

A simple large-scale purification of [alpha]2-adrenergic receptor-enriched membranes from human platelets is described. Binding of the antagonist [3H]yohimbine is enriched 3-5-fold compared to a crude membrane fraction. Binding of low concentrations of the partial agonist 3H-p-aminoclonidine is increased 15-20-fold due to a higher binding affinity for the purified membranes. A soluble inhibitor of 3H-p-aminoclonidine binding to purified membranes is found even in thrice-washed crude platelet membranes. The guanine nucleotides GDP and GTP are found to account for this inhibitory activity. Forskolin-stimulated adenylate cyclase activity is also enriched in the purified membrane fraction. Adenylate cyclase activity is inhibited by [alpha]2-agonist to a comparable extent in all membrane fractions. This membrane preparation should prove useful in studies of [alpha]2-adrenergic receptor mechanisms.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26295/1/0000380.pd

Diabetic neuropathy: inhibitory G protein dysfunction involves PKC-dependent phosphorylation of G oα

We examined the hypothesis that decreased inhibitory G protein function in diabetic neuropathy is associated with increased protein kinase C (PKC)-dependent phosphorylation of the G oα subunit. Streptozotocin-induced diabetic rats were studied between 4 and 8 weeks after onset of diabetes and compared with aged-matched healthy animals as controls. Opioid-mediated inhibition of forskolin-stimulated cyclic AMP was significantly less in dorsal root ganglia (DRGs) from diabetic rats compared with controls. Activation of PKC in DRGs from control rats was associated with a significant decrease in opioid-mediated inhibition of forskolin-stimulated cyclic AMP that was similar to the decrease in inhibition observed in DRGs from diabetic rats. Both basal and PKC-mediated labeling of G oα with 32 P i was significantly less in DRGs from diabetic rats, supporting increased endogenous PKC-dependent phosphorylation of G oα . Probing of immunoprecipitated G oα with an anti-phospho-serine/threonine specific antibody revealed a significant increase in baseline phosphorylation in diabetic DRGs. Activation of PKC produced a significant increase in phosphorylation in control DRGs but no significant increase in G oα in diabetic DRGs. Phosphorylation of PKC-α was increased, PKC-β II was unchanged and PKC-δ decreased in diabetic DRGs. These results suggest that diminished inhibitory G protein function observed in DRGs neurons from diabetic rats involves an isoform-specific PKC-dependent pathway.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66385/1/j.1471-4159.2003.01912.x.pd

Depicting a protein's two faces: GPCR classification by phylogenetic tree‐based HMMs

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/116379/1/feb2s0014579303011128.pd