Exercise preference in stroke survivors: a concept analysis

BackgroundExercise preference in stroke survivors is related to their adherence to long-term rehabilitation regimen and functional recovery. Although explored recently, the term exercise preference still lacks a clear definition.ObjectiveThe aim of this study is to conceptualize exercise preference in stroke survivors.MethodsThe Walker and Avant method was applied as a framework for the conceptual analysis of exercise preference. Data from 34 publications were collected using seven databases (PubMed, Web of Science, Embase, CINAHL, CNKI, Wanfang Data, and CBM) and applied in the analysis. The search period was from the inception of the database to April 30, 2023.ResultsExercise preference in stroke survivors was defined according to four attributes: priority of choice, behavioral tendency, affective priming, and patience in adherence. The common antecedents of the concept of exercise preference in stroke survivors were classified into patient-related, therapy-related, and environmental-related categories and the consequences were classified into three categories: patient-related, rehabilitation provider–related, and rehabilitation service system–related.ConclusionExercise preference in stroke survivors refers to the patient’s choice, tendency, affective response, and attitude toward engagement in the recommended rehabilitation regimen. It is beneficial for understanding the essential attributes of exercise preference in stroke survivors by clarifying the concept. In addition, it will facilitate the development of instruments for assessing exercise preference in stroke survivors and the construction of theory-based intervention programs that can improve adherence to exercise rehabilitation

Changes in axial length in anisometropic children wearing orthokeratology lenses

PurposeThere is a particular anisometropia occurring in one eye with myopia, while the other eye has very low myopia, emmetropia, or very low hyperopia. It is unclear how the binocular axial length changes when these children wear unilateral OK lenses only in the more myopic eyes. This study investigates the changes in the axial elongation of both eyes.MethodsThis is a 1-year retrospective study. In total, 148 children with myopic anisometropia were included. The more myopic eyes were wearing orthokeratology lenses (treated eyes), whereas the contralateral eyes were not indicated for visual correction (untreated eyes). The untreated eyes were classified into three subgroups based on the spherical equivalent refraction (SER): low myopia (≤ -0.50 D, n = 37), emmetropia (+0.49 to −0.49 D, n = 76), and low hyperopia (≥0.50 D, n = 35). Changes in the axial length (AL) were compared between the untreated and treated eyes and among the three subgroups.ResultsThe axial elongation was 0.14 ± 0.18 mm and 0.39 ± 0.27 mm in all treated and untreated eyes, respectively (p < 0.001). The interocular AL difference decreased significantly from 1.09 ± 0.45 mm at the baseline to 0.84 ± 0.52 mm at 1 year (p < 0.001). The baseline median (Q1, Q3) SER of the untreated eyes were −0.75 D (−0.56, −0.88 D), 0.00 D (0.00, −0.25 D), and +0.75 D (+1.00, +0.62 D) in low myopia, emmetropia, and low hyperopia subgroups, respectively. The axial elongation was 0.14 ± 0.18 mm, 0.15 ± 0.17 mm, and 0.13 ± 0.21 mm (p = 0.92) in the treated eyes and 0.44 ± 0.25 mm, 0.35 ± 0.24 mm, and 0.41 ± 0.33 mm in the untreated eyes (p = 0.11) after 1 year. Multivariate linear regression analyses only showed significant differences in axial elongation between the emmetropia and low myopia subgroups of untreated eyes (p = 0.04; p > 0.05 between other subgroups).ConclusionUnilateral orthokeratology lenses effectively reduced axial elongation in the more myopic eyes and reduced interocular AL differences in children with myopic anisometropia. The refractive state of the untreated eyes did not affect the axial elongation of the more myopic eye wearing the orthokeratology lens. In the untreated eyes, AL increased faster in the low myopia subgroup than in the emmetropia subgroup

Disruption of 5-hydroxytryptamine 1A receptor and orexin receptor 1 heterodimer formation affects novel G protein-dependent signaling pathways and has antidepressant effects in vivo

G protein-coupled receptor (GPCR) heterodimers are new targets for the treatment of depression. Increasing evidence supports the importance of serotonergic and orexin-producing neurons in numerous physiological processes, possibly via a crucial interaction between 5-hydroxytryptamine 1A receptor (5-HT1AR) and orexin receptor 1 (OX1R). However, little is known about the function of 5-HT1AR/OX1R heterodimers. It is unclear how the transmembrane domains (TMs) of the dimer affect its function and whether its modulation mediates antidepressant-like effects. Here, we examined the mechanism of 5-HT1AR/OX1R dimerization and downstream G protein-dependent signaling. We found that 5-HT1AR and OX1R form constitutive heterodimers that induce novel G protein-dependent signaling, and that this heterodimerization does not affect recruitment of β-arrestins to the complex. In addition, we found that the structural interface of the active 5-HT1AR/OX1R dimer transforms from TM4/TM5 in the basal state to TM6 in the active conformation. We also used mutation analyses to identify key residues at the interface (5-HT1AR R1514.40, 5-HT1AR Y1985.41, and OX1R L2305.54). Injection of chronic unpredictable mild stress (CUMS) rats with TM4/TM5 peptides improved their depression-like emotional status and decreased the number of endogenous 5-HT1AR/OX1R heterodimers in the rat brain. These antidepressant effects may be mediated by upregulation of BDNF levels and enhanced phosphorylation and activation of CREB in the hippocampus and medial prefrontal cortex. This study provides evidence that 5-HT1AR/OX1R heterodimers are involved in the pathological process of depression. Peptides including TMs of the 5-HT1AR/OX1R heterodimer interface are candidates for the development of compounds with fast-acting antidepressant-like effects

The Lysosomal v-ATPase-Ragulator Complex Is a Common Activator for AMPK and mTORC1, Acting as a Switch between Catabolism and Anabolism

林圣彩教授课题组长期致力于细胞信号转导的研究。近年来，该课题组潜心研究，不断攻关，取得了一系列重大成果，如揭示细胞如何应对生长因子缺乏的内在机理，发现了细胞自噬“路线图”、还发现了细胞如何感应“饥饿”信号AMP的信号传导通路等。其中，“发现细胞自噬‘路线图’”成果曾登上《科学》杂志，并入选2012年度“中国科学十大进展”。AMPK and mTOR play principal roles in governing metabolic programs; however, mechanisms underlying the coordination of the two inversely regulated kinases remain unclear. In this study we found, most surprisingly, that the late endosomal/lysosomal protein complex v-ATPase-Ragulator, essential for activation of mTORC1, is also required for AMPK activation. We also uncovered that AMPK is a residential protein of late endosome/lysosome. Under glucose starvation, the v-ATPase-Ragulator complex is accessible to AXIN/LKB1 for AMPK activation. Concurrently, the guanine nucleotide exchange factor (GEF) activity of Ragulator toward RAG is inhibited by AXIN, causing dissociation from endosome and inactivation of mTORC1. We have thus revealed that the v-ATPase-Ragulator complex is also an initiating sensor for energy stress and meanwhile serves as an endosomal docking site for LKB1-mediated AMPK activation by forming the v-ATPase-Ragulator-AXIN/LKB1-AMPK complex, thereby providing a switch between catabolism and anabolism. Our current study also emphasizes a general role of late endosome/lysosome in controlling metabolic programs

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Structural modeling of the intein and its parts.

<p>Computer-based modeling of the <i>Ssp</i> DnaX intein (A) and its parts (B, C, D) used the VMD program (<a href="http://www.ks.uiuc.edu/Research/vmd/" target="_blank">http://www.ks.uiuc.edu/Research/vmd/</a>) and the crystal structure of the <i>Ssp</i> DnaB mini-intein <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045355#pone.0045355-Ding1" target="_blank">[7]</a>. The 11-aa I_N part of the intein is shown in red. The C-terminal 6-aa part of the intein is shown in blue.</p

Effects of I_N size and Block B mutation on <i>trans</i>-splicing.

<p><i>A</i>. Schematic illustration of experimental designs. I_NL is the N-terminal 144-aa sequence of the <i>Ssp</i> DnaX intein. I_NLm and I_Cm are the same as I_NL and I_C, respectively, except that the conserved Block B sequence of the intein was mutated from TXXH to AXXA. Others are the same as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045355#pone-0045355-g001" target="_blank">Figure 1A</a>. <i>B</i>. <i>Trans</i>-splicing of I_CT with MI_NL. A mixture of the two precursor proteins was incubated at the specified temperatures for 20 hours to allow reaction, with the protein bands visualized by Western blotting using anti-T antibody. <i>C</i>. <i>Trans</i>-splicing of different precursor protein pairs listed in panel A. Each pair of precursor proteins was incubated together at room temperature for 20 hours, with the protein bands visualized by Western blotting using anti-T antibody. Names of only intein parts of the precursor proteins are specified on the top of the panel.</p

Cross-reactivity of I_C with I_N from different inteins.

<p><i>A.</i> Comparison of the amino acid sequences of I_N from <i>Ssp</i> DnaX intein (I_N), <i>Rma</i> DnaB intein (I_NRB), and <i>Ssp</i> GyrB intein (I_NSG). Identical and similar residues are marked with a | and a :, respectively. A gap (represented with a -) is introduced in the I_N sequence to maximize the sequence alignment. <i>B</i>. Analysis of <i>trans</i>-splicing reactions between I_C and I_NRB (or I_NSG) as specified on top. For <i>in vivo</i> analysis, MI_NRB (or MI_NSG) and I_CT proteins were co-expressed in <i>E. coli</i> cells, and total cellular proteins were analyzed by Western blotting using an anti-thioredoxin (Anti-T) antibody. For <i>in vitro</i> analysis, purified MI_NRB (or MI_NSG) and I_CT proteins were co-incubated at room temperature for 20 hours, and the reaction products were analyzed by Western blotting as above. Positions are marked for the precursor I_CT, splicing product MT, and C-cleavage product T. Size markers are shown on the left.</p

Detection of <i>trans</i>-splicing and C-cleavage activities.

<p><i>A</i>. Schematic illustration of the C-cleavage and <i>trans</i>-splicing reactions. Precursor protein I_CT is a fusion protein consisting of the 139-aa C-intein (I_C) of the <i>Ssp</i> DnaX split intein fused to a thioredoxin protein (T). Precursor protein MI_N is a fusion protein consisting of a maltose binding protein (M) and the 11-aa N-intein (I_N) of the <i>Ssp</i> DnaX split intein. <i>B</i>. Experimental analysis of the reactions. For analysis <i>in vivo</i>, MI_N and I_CT proteins were co-expressed in <i>E. coli</i> cells. Total cellular proteins before (NI) and after (I) the IPTG-induced expression were resolved by SDS-PAGE, and protein bands were visualized either by staining (Coomassie stained) or by Western blotting using an anti-thioredoxin (Anti-T) antibody. For analysis <i>in vitro</i>, the MI_N and I_CT proteins were separately produced and purified. These two proteins were then mixed and incubated at room temperature for 20 hours. Reaction products were analyzed and visualized by staining or Western blotting as above. Positions are indicated for the precursor proteins (MI_N and I_CT), the splicing product (MT), and the C-cleavage products (I_C and T). Size markers (Marker) are shown on the left. <i>C.</i> Effects of reaction times and temperatures. The <i>in vitro</i> reactions were carried out for the specified length of times and at the specified temperatures. Reaction products were analyzed by Western blotting as above.</p