Human Kif4A is a member of the Kinesin-4 family of kinesins. Kif4A is thought to be a
bona fide chromokinesin because it possesses a motor domain and associates with condensed chromosomes during ...mitosis. Genetic deletion of Kif4A promotes tumorigenic phenotypes in mouse embryonic cells. Kif4A is critical for mitotic regulation including chromosome condensation, spindle organization and cytokinesis. However, the precise chromatin-binding domain of Kif4A has not been characterized. Herein, we report the identification of two conserved motifs critical for chromatin-binding: the first leucine Zip motif (Zip1) of a leucine Zip/Basic/leucine Zip region (ZBZ) previously thought to be a nuclear localization signal (NLS), and a cysteine-rich (CR) motif within the C-terminal region of Kif4A. Furthermore, by depleting endogenous Kif4A via RNAi and concurrently expressing RNAi-resistant Kif4A versions, we observed that wild type Kif4A, but not the mutants deficient in DNA-binding (Zip1 or CR deleted) or ATPase activity (K94A point mutant), was able to rescue the RNAi-elicited abnormal mitotic profile. Taken together, our results show that both the Zip1 and CR motifs are important for Kif4A chromatin-binding and its mitotic function.
Although academic discourse has a reputation for its emotionless objectivity, the emotion of surprise is often expressed in scientific writing. Paradoxically, surprise is cognitive in nature and ...recognized as a knowledge emotion. Given the connection between surprise and knowledge-making, it is surprising that linguistic expressions of surprise (i.e., surprise markers) in academic discourse have received little research attention. This article reports on an empirical study of surprise markers in research articles. Informed by Charles Fillmore's frame semantics, the study identified and analyzed all the surprise markers in a corpus of 320 research articles. A total of 439 surprise markers were found to evoke seven interconnected semantic frames. These semantic frames contained eight conceptually distinct frame elements, five of which were markedly more frequent than the rest and appeared in 12.76–100% of the frame instances identified. Based on the results of the analyses, a genre-specific Surprise frame with five key frame elements was generalized and is presented in this article as a conceptual tool for understanding how surprise and its linguistic expressions partake in the construction of scientific knowledge. Recommendations are made about how the conceptual frame can inform future research.
•Drawing on frame semantics, this study examined surprise as a knowledge emotion.•Surprise markers were identified and classified in a corpus of 320 research articles.•Semantic frames evoked by the surprise markers and their relations were analyzed.•A surprise frame was generalized from the identified frames and key frame elements.•Recommendations are made about the frame as a conceptual tool for future research.
The clinical role and underlying mechanisms of valproic acid (VPA) on bone homeostasis remain controversial. Herein, we confirmed that VPA treatment was associated with decreased bone mass and bone ...mineral density (BMD) in both patients and mice. This effect was attributed to VPA-induced elevation in osteoclast formation and activity. Through RNA-sequencing, we observed a significant rise in precursor miR-6359 expression in VPA-treated osteoclast precursors in vitro, and further, a marked upregulation of mature miR-6359 (miR-6359) in vivo was demonstrated using quantitative real-time PCR (qRT-PCR) and miR-6359 fluorescent in situ hybridization (miR-6359-FISH). Specifically, the miR-6359 was predominantly increased in osteoclast precursors and macrophages but not in neutrophils, T lymphocytes, monocytes and bone marrow-derived mesenchymal stem cells (BMSCs) following VPA stimulation, which influenced osteoclast differentiation and bone-resorptive activity. Additionally, VPA-induced miR-6359 enrichment in osteoclast precursors enhanced reactive oxygen species (ROS) production by silencing the SIRT3 protein expression, followed by activation of the MAPK signaling pathway, which enhanced osteoclast formation and activity, thereby accelerating bone loss. Currently, there are no medications that can effectively treat VPA-induced bone loss. Therefore, we constructed engineered small extracellular vesicles (E-sEVs) targeting osteoclast precursors in bone and naturally carrying anti-miR-6359 by introducing of EXOmotif (CGGGAGC) in the 3'-end of the anti-miR-6359 sequence. We confirmed that the E-sEVs exhibited decent bone/osteoclast precursor targeting and exerted protective therapeutic effects on VPA-induced bone loss, but not on ovariectomy (OVX) and glucocorticoid-induced osteoporotic models, deepening our understanding of the underlying mechanism and treatment strategies for VPA-induced bone loss.
A typical microarray experiment has many sources of variation which can be attributed to biological and technical causes. Identifying sources of variation and assessing their magnitude, among other ...factors, are important for optimal experimental design. The objectives of this study were: (1) to estimate relative magnitudes of different sources of variation and (2) to evaluate agreement between biological and technical replicates.
We performed a microarray experiment using a total of 24 Affymetrix GeneChip arrays. The study included 4th mammary gland samples from eight 21-day-old Sprague Dawley CD female rats exposed to genistein (soy isoflavone). RNA samples from each rat were split to assess variation arising at labeling and hybridization steps. A general linear model was used to estimate variance components. Pearson correlations were computed to evaluate agreement between technical and biological replicates.
The greatest source of variation was biological variation, followed by residual error, and finally variation due to labeling when *.cel files were processed with dChip and RMA image processing algorithms. When MAS 5.0 or GCRMA-EB were used, the greatest source of variation was residual error, followed by biology and labeling. Correlations between technical replicates were consistently higher than between biological replicates.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Previous studies reported that mild inflammation promotes retinal ganglion cell (RGC) survival and axonal regeneration after optic nerve (ON) injury with involvement of infiltrating macrophages and ...neutrophils. Here we aimed to evaluate the involvement and regulation of the main inflammatory chemokine pathway CXCL5/CXCR2 in the inflammation-mediated RGC survival and axonal regeneration in mice after ON injury.
The expressions and cellular locations of CXCL5 and CXCR2 were confirmed in mouse retina. Treatment effects of recombinant CXCL5 and CXCR2 antagonist SB225002 were studied in the explant culture and the ON injury model with or without lens injury. The number of RGCs, regenerating axons, and inflammatory cells were determined, and the activation of Akt andSTAT3 signaling pathways were evaluated.
Cxcr2 and Cxcl5 expressions were increased after ON and lens injury. Addition of recombinant CXCL5 promoted RGC survival and neurite outgrowth in retinal explant culture with increase in the number of activated microglia, which was inhibited by SB225002 or clodronate liposomes. Recombinant CXCL5 also alleviated RGC death and promoted axonal regeneration in mice after ON injury, and promoted the lens injury-induced RGC protection with increase in the number of activated CD68+ cells. SB225002 inhibited lens injury-induced cell infiltration and activation, and attenuated the promotion effect on RGC survival and axonal regeneration through reduction of lens injury-induced Akt activation.
CXCL5 promotes RGC survival and axonal regeneration after ON injury and further enhances RGC protection induced by lens injury with CD68+ cell activation, which is attenuated by CXCR2 antagonist. CXCL5/CXCR2 could be a potential therapeutic target for RGC survival promotion after ON injury.
•CXCL5 promotes in vitro RGC survival, neurite outgrowth and microglia activation.•Intravitreal injection of CXCL5 reduces RGC death and promotes axonal regeneration after ON injury.•Intravitreal injection of CXCL5 enhances the promotion effect of lens injury-mediated RGC protection after ON injury.•CXCR2 inhibition attenuates the promotion effect of lens injury-mediated RGC protection after ON injury.•CXCL5/CXCR2 may modulate optic nerve repair by regulating inflammatory cell infiltration and microglia activation.
An androst-4-ene-3,17-dione (AD)-producing mutant, AD1 and an androsta-1,4-diene-3,17-dione (ADD)-producing mutant, PD3 were derived from a cholesterol-, phytosterol-assimilating bacterium
...Mycobacterium sp. B-3805S and a cholesterol-assimilating bacterium
Mycobacterium sp. NRRL B-3683, respectively, using nitrosoguanidine (NTG) mutagenesis. Production of AD or ADD from phytosterol by the two mutants was investigated in a 5-L surface-aeration microprocessor-controlled fermentor at 30
°C. It was found that the maximum conversion of phytosterol to AD or ADD was 67.9 or 70.6%, respectively. Control of glucose concentration in the fermentation culture is an important parameter that affects production of AD or ADD as a sole product from phytosterol. The major components of phytosterol such as campesterol, stigmasterol and β-sitosterol were proportionally consumed by the two mutants without nutrient preference. AD or ADD were isolated from the fermentation broth by the addition of Amberlite XAD-7 resin and were further purified by silica gel column chromatography. After crystallization in methanol, the purified AD or ADD was obtained as needle crystals, which were identical to authentic AD or ADD by physical and instrumental analyses.
This article examines the biography, literature, and religious thought of Shi Tiesheng (1951–2010), arguably the most influential author with a disability in contemporary China. Using the definition ...of “theology” in its broad sense, it argues that Shi has developed a kind of disability theology through his non-fiction and fictional works, though he never claimed to be a theologian or saw his works as theological. This theology borrows terms and ideas from Christianity, but also follows the syncretic tradition of Chinese religions. In contemporary China, where religions have been marginalized, religious vocabulary and contemplation helped Shi break free of the narrative assigned to people with disabilities by the atheist state.
Disability Theology Despite Itself Chen, Lang
Journal of disability & religion,
10/1/2020, 2020-10-01, Letnik:
24, Številka:
4
Journal Article
Recenzirano
This article examines the biography, literature, and religious thought of Shi Tiesheng (1951-2010), arguably the most influential author with a disability in contemporary China. Using the definition ...of "theology" in its broad sense, it argues that Shi has developed a kind of disability theology through his non-fiction and fictional works, though he never claimed to be a theologian or saw his works as theological. This theology borrows terms and ideas from Christianity, but also follows the syncretic tradition of Chinese religions. In contemporary China, where religions have been marginalized, religious vocabulary and contemplation helped Shi break free of the narrative assigned to people with disabilities by the atheist state.
Studies of the novel coronavirus-induced disease COVID-19 in Wuhan, China, have elucidated the epidemiological and clinical characteristics of this disease in the general population. The present ...investigation summarizes the clinical characteristics and early prognosis of COVID-19 infection in a cohort of patients with fractures.
Data on 10 patients with a fracture and COVID-19 were collected from 8 different hospitals located in the Hubei province from January 1, 2020, to February 27, 2020. Analyses of early prognosis were based on clinical outcomes and trends in laboratory results during treatment.
All 10 patients presented with limited activity related to the fracture. The most common signs were fever, cough, and fatigue at the time of presentation (7 patients each). Other, less common signs included sore throat (4 patients), dyspnea (5 patients), chest pain (1 patient), nasal congestion (1 patient), headache (1 patient), dizziness (3 patients), abdominal pain (1 patient), and vomiting (1 patient). Lymphopenia (<1.0 × 10 cells/L) was identified in 6 of 10 patients, 9 of 9 patients had a high serum level of D-dimer, and 9 of 9 patients had a high level of C-reactive protein. Three patients underwent surgery, whereas the others were managed nonoperatively because of their compromised status. Four patients died on day 8 (3 patients) or day 14 (1 patient) after admission. The clinical outcomes for the surviving patients are not yet determined.
The clinical characteristics and early prognosis of COVID-19 in patients with fracture tended to be more severe than those reported for adult patients with COVID-19 without fracture. This finding may be related to the duration between the development of symptoms and presentation. Surgical treatment should be carried out cautiously or nonoperative care should be chosen for patients with fracture in COVID-19-affected areas, especially older individuals with intertrochanteric fractures.
Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
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