126 research outputs found
STI-GAN: multimodal pedestrian trajectory pre-diction using spatiotemporal interactions and a generative adversarial network
Bifacial dye-sensitized solar cells : a strategy to enhance overall efficiency based on transparent polyaniline electrode
Dye-sensitized solar cell (DSSC) is a promising solution to global energy and environmental problems
because of its clean, low-cost, high efficiency, good durability, and easy fabrication. However, enhancing the
efficiency of the DSSC still is an important issue. Here we devise a bifacial DSSC based on a transparent
polyaniline (PANI) counter electrode (CE). Owing to the sunlight irradiation simultaneously from the front
and the rear sides, more dye molecules are excited and more carriers are generated, which results in the
enhancement of short-circuit current density and therefore overall conversion efficiency. The photoelectric
properties of PANI can be improved by modifying with 4-aminothiophenol (4-ATP). The bifacial DSSC
with 4-ATP/PANI CE achieves a light-to-electric energy conversion efficiency of 8.35%, which is increased
by ,24.6% compared to the DSSC irradiated from the front only. This new concept along with promising
results provides a new approach for enhancing the photovoltaic performances of solar cells.The authors acknowledge the financial joint support by the National High Technology Research and Development Program of China (No. 2009AA03Z217), the National Natural Science Foundation of China (nos. 90922028, U1205112, 51002053, 61306077), Seed Fund from Ocean University of China, and Fundamental Research Funds for the Central Universities (201313001)
Solution structure of the second bromodomain of Brd2 and its specific interaction with acetylated histone tails
<p>Abstract</p> <p>Background</p> <p>Brd2 is a transcriptional regulator and belongs to BET family, a less characterized novel class of bromodomain-containing proteins. Brd2 contains two tandem bromodomains (BD1 and BD2, 46% sequence identity) in the N-terminus and a conserved motif named ET (extra C-terminal) domain at the C-terminus that is also present in some other bromodomain proteins. The two bromodomains have been shown to bind the acetylated histone H4 and to be responsible for mitotic retention on chromosomes, which is probably a distinctive feature of BET family proteins. Although the crystal structure of Brd2 BD1 is reported, no structure features have been characterized for Brd2 BD2 and its interaction with acetylated histones.</p> <p>Results</p> <p>Here we report the solution structure of human Brd2 BD2 determined by NMR. Although the overall fold resembles the bromodomains from other proteins, significant differences can be found in loop regions, especially in the ZA loop in which a two amino acids insertion is involved in an uncommon <it>π</it>-helix, termed <it>π</it>D. The helix <it>π</it>D forms a portion of the acetyl-lysine binding site, which could be a structural characteristic of Brd2 BD2 and other BET bromodomains. Unlike Brd2 BD1, BD2 is monomeric in solution. With NMR perturbation studies, we have mapped the H4-AcK12 peptide binding interface on Brd2 BD2 and shown that the binding was with low affinity (2.9 mM) and in fast exchange. Using NMR and mutational analysis, we identified several residues important for the Brd2 BD2-H4-AcK12 peptide interaction and probed the potential mechanism for the specific recognition of acetylated histone codes by Brd2 BD2.</p> <p>Conclusion</p> <p>Brd2 BD2 is monomeric in solution and dynamically interacts with H4-AcK12. The additional secondary elements in the long ZA loop may be a common characteristic of BET bromodomains. Surrounding the ligand-binding cavity, five aspartate residues form a negatively charged collar that serves as a secondary binding site for H4-AcK12. We suggest that Brd2 BD1 and BD2 may possess distinctive roles and cooperate to regulate Brd2 functions. The structure basis of Brd2 BD2 will help to further characterize the functions of Brd2 and its BET members.</p
Stat3 isoforms, α and β, demonstrate distinct intracellular dynamics with prolonged nuclear retention of Stat3β mapping to its unique C-terminal end
Two isoforms of Stat3 (signal transducer and activator of transcription 3) are expressed in cells, alpha (p92) and beta (p83), both derived from a single gene by alternative mRNA splicing. The 55-residue C-terminal transactivation domain of Stat3alpha is deleted in Stat3beta and replaced by seven unique C-terminal residues (CT7) whose function remains uncertain. We subcloned the open reading frames of Stat3alpha and Stat3beta into the C terminus of green fluorescent protein (GFP). Fluorescent microscopic analysis of HEK293T cells transiently transfected with GFP-Stat3alpha or GFP-Stat3beta revealed similar kinetics and cytokine concentration dependence of nuclear accumulation; these findings were confirmed by high throughput microscope analysis of murine embryonic fibroblasts that lacked endogenous Stat3 but stably expressed either GFP-Stat3alpha or GFP-Stat3beta. However, although time to half-maximal cytoplasmic reaccumulation after cytokine withdrawal was 15 min for GFP-Stat3alpha, it was >180 min for GFP-Stat3beta. Furthermore, although the intranuclear mobility of GFP-Stat3alpha was rapid and increased with cytokine stimulation, the intranuclear mobility of GFP-Stat3beta in unstimulated cells was slower than that of GFP-Stat3alpha in unstimulated cells and was slowed further following cytokine stimulation. Deletion of the unique CT7 domain from Stat3beta eliminated prolonged nuclear retention but did not alter its intranuclear mobility. Thus, Stat3alpha and Stat3beta have distinct intracellular dynamics, with Stat3beta exhibiting prolonged nuclear retention and reduced intranuclear mobility especially following ligand stimulation. Prolonged nuclear retention, but not reduced intranuclear mobility, mapped to the CT7 domain of Stat3beta
Efficacy of practising Tai Chi for older people with mild dementia: Protocol for a randomised controlled study
© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. Introduction Many studies suggest that Tai Chi exercise is a safe and appropriate mind-body exercise for older people and effectively slows down age-related cognitive decline. A set of bespoke Tai Chi exercise named 'Cognition Protecting Tai Chi' (CPT) has been created for older people with cognitive impairments by the research team of geriatricians, neurologists, rehabilitation specialists, experts of sports medicine and experienced practitioners of traditional Chinese medicine. This trial is designed to evaluate its effects on cognitive function, behaviour/moods, risk of falls and activities of daily living of the participants with mild dementia. Methods and analysis A randomised controlled study will be conducted. Eighty participants with mild dementia will be recruited and randomly allocated to an intervention group and a control group. The intervention group will practice the CPT exercise three times a week for 20 min each time under the guidance of professional therapists. The control group will continue receiving their routine treatments. The duration of this study will be 10 months. All participants will be assessed with a battery of neuropsychological and functional evaluations, which include Mini Mental State Examination, Montreal Cognitive Assessment, the WHO-University of California Los Angeles-Auditory Verbal Learning test (WHO-UCLA-AVLT), Trail Making Test (TMT), Geriatric Depression Scale, Neuropsychological Inventory and Barthel Index, at the baseline, 5 and 10 months during the study period. Fall incident will also be recorded. The primary outcome will be the WHO-UCLA-AVLT delayed recall score. The secondary outcome will be the TMT score. Ethics and dissemination This study has been approved by the ethical review committee of the Beijing Geriatric Hospital (protocol number: 2015-021). Informed consent will be obtained from all participants or their guardians. The authors intend to submit the findings of the study to peer-reviewed journals or academic conferences to be published
Fluctuation of primary motor cortex excitability during cataplexy in narcolepsy
Objective Cataplexy is a complicated and dynamic process in narcolepsy type 1 (NT1) patients. This study aimed to clarify the distinct stages during a cataplectic attack and identify the changes of the primary motor cortex (PMC) excitability during these stages. Methods Thirty-five patients with NT1 and 29 healthy controls were recruited to this study. Cataplectic stages were distinguished from a cataplectic attack by video-polysomnogram monitoring. Transcranial magnetic stimulation motor-evoked potential (TMS-MEP) was performed to measure the excitability of PMC during quiet wakefulness, laughter without cataplexy, and each cataplectic stage. Results Based on the video and electromyogram observations, a typical cataplectic attack (CA) process is divided into four stages: triggering (CA1), resisting (CA2), atonic (CA3), and recovering stages (CA4). Compared with healthy controls, NT1 patients showed significantly decreased intracortical facilitation during quiet wakefulness. During the laughter stage, both patients and controls showed increased MEP amplitude compared with quiet wakefulness. The MEP amplitude significantly increased even higher in CA1 and 2, and then dramatically decreased in CA3 accompanied with prolonged MEP latency compared with the laughter stage and quiet wakefulness. The MEP amplitude and latency gradually recovered during CA4. Interpretation This study identifies four stages during cataplectic attack and reveals the existence of a resisting stage that might change the process of cataplexy. The fluctuation of MEP amplitude and MEP latency shows a potential participation of PMC and motor control pathway during cataplexy, and the increased MEP amplitude during CA1 and 2 strongly implies a compensatory mechanism in motor control that may resist or avoid cataplectic attack
The Mitochondrial Deoxyguanosine Kinase is Required for Cancer Cell Stemness in Lung Adenocarcinoma
The mitochondrial deoxynucleotide triphosphate (dNTP) is maintained by the mitochondrial deoxynucleoside salvage pathway and dedicated for the mtDNA homeostasis, and the mitochondrial deoxyguanosine kinase (DGUOK) is a rate-limiting enzyme in this pathway. Here, we investigated the role of the DGUOK in the self-renewal of lung cancer stem-like cells (CSC). Our data support that DGUOK overexpression strongly correlates with cancer progression and patient survival. The depletion of DGUOK robustly inhibited lung adenocarcinoma tumor growth, metastasis, and CSC self-renewal. Mechanistically, DGUOK is required for the biogenesis of respiratory complex I and mitochondrial OXPHOS, which in turn regulates CSC self-renewal through AMPK-YAP1 signaling. The restoration of mitochondrial OXPHOS in DGUOK KO lung cancer cells using NDI1 was able to prevent AMPK-mediated phosphorylation of YAP and to rescue CSC stemness. Genetic targeting of DGUOK using doxycycline-inducible CRISPR/Cas9 was able to markedly induce tumor regression. Our findings reveal a novel role for mitochondrial dNTP metabolism in lung cancer tumor growth and progression, and implicate that the mitochondrial deoxynucleotide salvage pathway could be potentially targeted to prevent CSC-mediated therapy resistance and metastatic recurrence
Analysis of chromosomal structural variations in patients with recurrent spontaneous abortion using optical genome mapping
Background and aims: Certain chromosomal structural variations (SVs) in biological parents can lead to recurrent spontaneous abortions (RSAs). Unequal crossing over during meiosis can result in the unbalanced rearrangement of gamete chromosomes such as duplication or deletion. Unfortunately, routine techniques such as karyotyping, fluorescence in situ hybridization (FISH), chromosomal microarray analysis (CMA), and copy number variation sequencing (CNV-seq) cannot detect all types of SVs. In this study, we show that optical genome mapping (OGM) quickly and accurately detects SVs for RSA patients with a high resolution and provides more information about the breakpoint regions at gene level.Methods: Seven couples who had suffered RSA with unbalanced chromosomal rearrangements of aborted embryos were recruited, and ultra-high molecular weight (UHMW) DNA was isolated from their peripheral blood. The consensus genome map was created by de novo assembly on the Bionano Solve data analysis software. SVs and breakpoints were identified via alignments of the reference genome GRCh38/hg38. The exact breakpoint sequences were verified using either Oxford Nanopore sequencing or Sanger sequencing.Results: Various SVs in the recruited couples were successfully detected by OGM. Also, additional complex chromosomal rearrangement (CCRs) and four cryptic balanced reciprocal translocations (BRTs) were revealed, further refining the underlying genetic causes of RSA. Two of the disrupted genes identified in this study, FOXK2 [46,XY,t(7; 17)(q31.3; q25)] and PLXDC2 [46,XX,t(10; 16)(p12.31; q23.1)], had been previously shown to be associated with male fertility and embryo transit.Conclusion: OGM accurately detects chromosomal SVs, especially cryptic BRTs and CCRs. It is a useful complement to routine human genetic diagnostics, such as karyotyping, and detects cryptic BRTs and CCRs more accurately than routine genetic diagnostics
Effects of cumulus cell removal time during in vitro fertilization on embryo quality and pregnancy outcomes: a prospective randomized sibling-oocyte study
The impact of land-cover change on flood peaks in peatland basins
In headwater peatlands, saturation-excess overland flow is a dominant source of river discharge. Human modifications to headwater peatlands result in vegetation cover change but there is a lack of understanding about how the spatial distribution of such change impacts flood peaks. A fully distributed version of TOPMODEL with an overland flow velocity module was used to simulate flood response for three upland peat basins. Bare peat strips adjacent to channels resulted in a higher and faster flow peak; for a 20 mm/hr rainfall event, with bare riparian zones covering 10% of the basin area, peaks were increased, compared to the current hydrograph, by 12.8%, 1.8% and 19.6% in the three basins. High density Sphagnum ground cover over the same riparian zones reduced flow peaks (e.g. by 10.1%, 1.8% and 13.4% for the 20 mm hr-1 event) compared to the current hydrograph. With similar total areas of land-cover change, the size of randomly located patches of changed cover had no effect on peak flow for patch sizes up to 40000 m2. However, cover changes on gentle slope areas generally resulted in a larger change in peak flow when compared with the same changes on steeper slopes. Considering all results for the same proportion of catchment area that undergoes change, land-cover change along narrow riparian buffer strips had the highest impact on river flow. Thus, the protection and revegetation of damaged riparian areas in upland peat catchments may be highly beneficial for flood management
- …