USE1

Last update 08 May 2025

Basic Info

Synonyms

D12, MDS032, p31

+ [7]

Introduction

SNARE that may be involved in targeting and fusion of Golgi-derived retrograde transport vesicles with the ER.

100 Clinical Results associated with USE1

100 Translational Medicine associated with USE1

0 Patents (Medical) associated with USE1

230

Literatures (Medical) associated with USE1

01 May 2025·Respiratory Medicine

Associations of comorbid heart disease and depression/anxiety with multidimensional breathlessness in COPD – A cross-sectional study

Article

Author: Ekström, Magnus ; Hasselgren, Mikael ; Nager, Anna ; Sundh, Josefin ; Lisspers, Karin ; Ställberg, Björn ; Janson, Christer ; Giezeman, Maaike ; Kisiel, Marta A ; Sandelowsky, Hanna ; Montgomery, Scott ; Eliason, Gabriella

BACKGROUNDComorbid conditions and breathlessness are associated with poor outcomes in chronic obstructive pulmonary disease (COPD). We evaluated the associations of comorbid heart disease and depression/anxiety with breathlessness in daily life among people with COPD.METHODSCross-sectional analysis from the PRAXIS cohort in central Sweden. Data on patient characteristics and the modified Medical Research Council (mMRC) and Dyspnea-12 breathlessness instruments (D-12) were obtained from questionnaires in 2022. Lung function data were collected from record review. Outcome variables were clinically significant breathlessness defined as mMRC≥2 and D-12 total (>2.7), physical (>1.4) and affective (>1.2) scores above published minimal clinical important differences. Associations of heart disease and depression/anxiety with each outcome were analyzed using multivariable Poisson regression adjusted for relevant confounders.RESULTSIn 522 included patients, mMRC ≥2 was present in 59 % and increased D-12 total, physical and affective domain scores in 69 %, 74 %, and 50 %, respectively. Heart disease was independently associated with mMRC (relative risk ratio [95 % confidence interval] 1.34 [1.17-1.53]), D12 physical domain (1.12[1.02-1.24]) and D-12 affective domain (1.20[1.02-1.42]). Depression/anxiety was independently associated with increased D-12 affective domain (1.25[1.04-1.49]). In addition, previous exacerbations and GOLD stage 3-4 were associated with mMRC and D-12, respectively.CONCLUSIONIn COPD, comorbid heart disease is associated with both activity-related breathlessness and with physical and affective domains of breathlessness while depression/anxiety is associated with the affective domain of breathlessness. As the influence of different dimensions of breathlessness may differ according to comorbidity the D-12 instrument adds more information when assessing breathlessness in patients with COPD.

01 Mar 2025·Journal of Molecular Biology

Dynamic Coupling and Entropy Changes in KRAS G12D Mutation: Insights into Molecular Flexibility, Allostery and Function

Article

Author: Yuret, Deniz ; Erman, Burak ; Hacisuleyman, Aysima

The oncogenic G12D mutation in KRAS is a major driver of cancer progression, yet the complete mechanism by which this mutation alters protein dynamics and function remains incompletely understood. Here, we investigate how the G12D mutation alters KRAS's conformational landscape and residue-residue interactions using molecular dynamics simulations coupled with entropy calculations and mutual information (MI) analysis. We demonstrate that the mutation increases local entropy at key functional residues (D12, Y32, G60, and Q61), and introduces new peaks to the Ramachandran angles, disrupting the precise structural alignment necessary for GTP hydrolysis. Notably, while individual residue entropy increases, joint entropy analysis shows a complex reorganization pattern. MI analysis identifies enhanced dynamic coupling between distant residues, suggesting that the mutation establishes new long-range interactions that stabilize the active state. These findings show how G12D mutation redefines KRAS's dynamic network, leading to persistent activation through enhanced residue coupling rather than mere local disruption. Our results suggest novel therapeutic strategies focused on modulating protein dynamics rather than targeting specific binding sites, potentially offering new approaches to combat KRAS-driven cancers.

01 Jan 2025·European Journal of Medicinal Chemistry

Natural phenol carbamates: Selective BuChE/FAAH dual inhibitors show neuroprotection in an Alzheimer's disease mouse model

Article

Author: Rong, Kuanrong ; Tang, Wenjian ; Jiang, Xiaorui ; Wu, Xiaoming ; Gao, Shan ; Yang, Jing ; Zhang, Jing ; Zhao, Jie ; Li, Ziyun

FAAH inhibition can indirectly enhance endocannabinoid signaling to therapeutic levels, effectively preventing or slowing its progression of Alzheimer's disease (AD). Hence, the search for effective dual FAAH/cholinesterase inhibitors is considerable need for disease-modifying therapies. To this aim, we designed, synthesized, and tested three series of natural phenol carbamates. The majority of carbamates proved to be potent on a single target, amongst them, compound D12 containing paeonol motif was identified as an effective dual BuChE/FAAH inhibitor, with well-balanced nanomolar activity (IC₅₀ = 81 and 400 nM for hBuChE and hFFAH, respectively). D12 possessed BBB penetrating ability, benign safety, neuroprotection and pseudo-irreversible BuChE inhibition (K_d = 2.11 μM, k₂ = 2.27 min^-1), showing good drug-like properties. D12 also modulated the BV2 microglial polarization to inhibit neuroinflammation. In vivo study verified that D12 improved Aβ_1-41-induced learning impairments in AD mouse model for both short- and long-term memory responses. Thus, the dual activity of D12 could lead to a potentially more effective treatment for the counteraction of AD progression.

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