Sleep duration and efficiency are associated with plasma amyloid-ß in non-demented older people.

STUDY OBJECTIVES: This study aims to investigate the extent to which sleep duration and efficiency are associated with plasma amyloid-ß (Aß) levels in non-demented older people. METHODS: This study is a cross-sectional analysis of 305 non-demented older people. Sleep duration and efficiency were assessed used the Pittsburgh Sleep Quality Index. Levels of plasma Aß were determined by sandwich enzyme-linked immunosorbent assay technique. Associations between sleep variables and plasma Aß levels were evaluated with multivariable linear regression analysis. RESULTS: Compared to those with sleep duration > 7 h, participants with sleep duration < 6 h had a higher plasma Aß42 level (ß = 0.495, 95% CI 0.077~0.913, p = 0.021) and Aß42/Aß40 ratio (ß = 0.101, 95% CI 0.058~0.144, p < 0.001). Compared to those with sleep efficiency ≥ 85%, participants with lower sleep efficiency (65~74%, <65%) had a higher level of plasma Aß42 (<65%: ß = 0.627, 95% CI 0.147~1.108, p = 0.011) and Aß42/Aß40 ratio (65~74%: ß = 0.052, 95% CI 0.007~0.097, p = 0.026; <65%: ß = 0.117, 95% CI 0.067~0.168, p < 0.001). CONCLUSIONS: These findings indicated that short sleep duration and low sleep efficiency were associated with a high level of Aß42. A better comprehending of the link between sleep and plasma Aß levels may lead to effective sleep-based intervention to reduce the risk of Alzheimer's disease.

Variation of microRNA expression in the human placenta driven by population identity and sex of the newborn.

BACKGROUND: Analysis of lymphocyte cell lines revealed substantial differences in the expression of mRNA and microRNA (miRNA) among human populations. The extent of such population-associated differences in actual human tissues remains largely unexplored. The placenta is one of the few solid human tissues that can be collected in substantial numbers in a controlled manner, enabling quantitative analysis of transient biomolecules such as RNA transcripts. Here, we analyzed microRNA (miRNA) expression in human placental samples derived from 36 individuals representing four genetically distinct human populations: African Americans, European Americans, South Asians, and East Asians. All samples were collected at the same hospital following a unified protocol, thus minimizing potential biases that might influence the results. RESULTS: Sequence analysis of the miRNA fraction yielded 938 annotated and 70 novel miRNA transcripts expressed in the placenta. Of them, 82 (9%) of annotated and 11 (16%) of novel miRNAs displayed quantitative expression differences among populations, generally reflecting reported genetic and mRNA-expression-based distances. Several co-expressed miRNA clusters stood out from the rest of the population-associated differences in terms of miRNA evolutionary age, tissue-specificity, and disease-association characteristics. Among three non-environmental influenced demographic parameters, the second largest contributor to miRNA expression variation after population was the sex of the newborn, with 32 miRNAs (3% of detected) exhibiting significant expression differences depending on whether the newborn was male or female. Male-associated miRNAs were evolutionarily younger and correlated inversely with the expression of target mRNA involved in neuron-related functions. In contrast, both male and female-associated miRNAs appeared to mediate different types of hormonal responses. Demographic factors further affected reported imprinted expression of 66 placental miRNAs: the imprinting strength correlated with the mother's weight, but not height. CONCLUSIONS: Our results showed that among 12 assessed demographic variables, population affiliation and fetal sex had a substantial influence on miRNA expression variation among human placental samples. The effect of newborn-sex-associated miRNA differences further led to expression inhibition of the target genes clustering in specific functional pathways. By contrast, population-driven miRNA differences might mainly represent neutral changes with minimal functional impacts.

Lipidome alterations in human prefrontal cortex during development, aging, and cognitive disorders.

Lipids are essential to brain functions, yet they remain largely unexplored. Here we investigated the lipidome composition of prefrontal cortex gray matter in 396 cognitively healthy individuals with ages spanning 100 years, as well as 67 adult individuals diagnosed with autism (ASD), schizophrenia (SZ), and Down syndrome (DS). Of the 5024 detected lipids, 95% showed significant age-dependent concentration differences clustering into four temporal stages, and resulting in a gradual increase in membrane fluidity in individuals ranging from newborn to nonagenarian. Aging affects 14% of the brain lipidome with late-life changes starting predominantly at 50-55 years of age-a period of general metabolic transition. All three diseases alter the brain lipidome composition, leading-among other things-to a concentration decrease in glycerophospholipid metabolism and endocannabinoid signaling pathways. Lipid concentration decreases in SZ were further linked to genetic variants associated with disease, indicating the relevance of the lipidome changes to disease progression.

Predominant patterns of splicing evolution on human, chimpanzee and macaque evolutionary lineages.

Although splicing is widespread and evolves rapidly among species, the mechanisms driving this evolution, as well as its functional implications, are not yet fully understood. We analyzed the evolution of splicing patterns based on transcriptome data from five tissues of humans, chimpanzees, rhesus macaques and mice. In total, 1526 exons and exon sets from 1236 genes showed significant splicing differences among primates. More than 60% of these differences represent constitutive-to-alternative exon transitions while an additional 25% represent changes in exon inclusion frequency. These two dominant evolutionary patterns have contrasting conservation, regulation and functional features. The sum of these features indicates that, despite their prevalence, constitutive-to-alternative exon transitions do not substantially contribute to long-term functional transcriptome changes. Conversely, changes in exon inclusion frequency appear to be functionally relevant, especially for changes taking place in the brain on the human evolutionary lineage.

Accurate prediction of species-specific 2-hydroxyisobutyrylation sites based on machine learning frameworks.

Lysine 2-hydroxyisobutyrylation (Khib) is a newly discovered post-translational modification (PTM) across eukaryotes and prokaryotes in recent years, which plays a significant role in diverse cellular functions. Accurate prediction of Khib sites is a first-crucial step to decipher its molecular mechanism and urgently needed. In this work, based on a large benchmark datasets in multi-species, a novel online species-specific prediction tool, namely KhibPred, was developed to identify Khib sites. Four types of feature strategies, including sequence-based information, physicochemical properties and evolutionary-derived information, were applied to represent a wide range of protein sequences, and the random forest was used to build the optimal feature datasets. Moreover, six representative machine learning (ML) methods were trained and comprehensively discussed and compared for each organism. Data analyses suggested that the unique protein sequence preferences were discovered for each species. When evaluated on independent test datasets, the area under the receiver operating characteristic curves (AUCs) achieved 0.807, 0.781, 0.825 and 0.831 for Saccharomyces cerevisiaes, Physcomitrella patens, Rice Seeds and HeLa cells, respectively. The satisfactory results imply that KhibPred is a promising computational tool. The online predictor can be freely available at: http://bioinfo.ncu.edu.cn/KhibPred.aspx.

Design and synthesis of a vanadate-based ratiometric fluorescent probe for sequential recognition of Cu2+ ions and biothiols.

A novel YVO4:Eu3+@CDs core-shell nanomaterial with two main emission peaks at 405 and 617 nm was synthesized through a simple mixing method, in which the carbon quantum dots (CDs) self-assembled with the YVO4:Eu3+ nanoparticle, due to the high affinity of oxygen-containing groups such as -COOH or -OH of CDs to the metal ions on the surface of YVO4:Eu3+. The red fluorescence of YVO4:Eu3+@CDs located at 617 nm can be quenched by Cu2+ ions efficiently, while the blue emission remains invariable; based on this, we construct a ratio fluorescent probe YVO4:Eu3+@CDs for Cu2+ ion detection, in which the blue emission of CDs is selected as the reference signal, and the red emission of YVO4:Eu3+ acts as an output signal. Furthermore, the addition of biothiol recovers the quenched red fluorescence quickly, which can be completed in 18 minutes. Thus, YVO4:Eu3+@CDs can also be used as a 'turn on' ratio fluorescent probe for biothiol rapid detection. Taking l-cysteine (l-Cys) as the model, the fluorescence intensity of the 617 nm peak increases with increasing Cys, and the ratio of F617/F405 is linear to the concentration of Cys in the range of 0.1 µM to 10 µM with a detection limit of 41 nM. Compared with these single wavelength emission biothiol fluorescent probes, an obvious change in the fluorescence color from blue to pink can be conveniently observed by the naked eye under a UV lamp. Meanwhile, this ratiometric probe has also been demonstrated to be used for the visual identification of biothiols in real blood serum samples.

Curved Fragmented Graphenic Hierarchical Architectures for Extraordinary Charging Capacities.

An approach to assemble hierarchically ordered 3D arrangements of curved graphenic nanofragments for energy storage devices is described. Assembling them into well-defined interconnected macroporous networks, followed by removal of the template, results in spherical macroporous, mesoporous, and microporous carbon microball (3MCM) architectures with controllable features spanning nanometer to micrometer length scales. These structures are ideal porous electrodes and can serve as lithium-ion battery (LIB) anodes as well as capacitive deionization (CDI) devices. The LIBs exhibit high reversible capacity (up to 1335 mAh g-1 ), with great rate capability (248 mAh g-1 at 20 C) and a long cycle life (60 cycles). For CDI, the curved graphenic networks have superior electrosorption capacity (i.e., 5.17 mg g-1 in 0.5 × 10-3 m NaCl) over conventional carbon materials. The performance of these materials is attributed to the hierarchical structure of the graphenic electrode, which enables faster ion diffusion and low transport resistance.

Incorporating key position and amino acid residue features to identify general and species-specific Ubiquitin conjugation sites.

MOTIVATION: Systematic dissection of the ubiquitylation proteome is emerging as an appealing but challenging research topic because of the significant roles ubiquitylation play not only in protein degradation but also in many other cellular functions. High-throughput experimental studies using mass spectrometry have identified many ubiquitylation sites, primarily from eukaryotes. However, the vast majority of ubiquitylation sites remain undiscovered, even in well-studied systems. Because mass spectrometry-based experimental approaches for identifying ubiquitylation events are costly, time-consuming and biased toward abundant proteins and proteotypic peptides, in silico prediction of ubiquitylation sites is a potentially useful alternative strategy for whole proteome annotation. Because of various limitations, current ubiquitylation site prediction tools were not well designed to comprehensively assess proteomes. RESULTS: We present a novel tool known as UbiProber, specifically designed for large-scale predictions of both general and species-specific ubiquitylation sites. We collected proteomics data for ubiquitylation from multiple species from several reliable sources and used them to train prediction models by a comprehensive machine-learning approach that integrates the information from key positions and key amino acid residues. Cross-validation tests reveal that UbiProber achieves some improvement over existing tools in predicting species-specific ubiquitylation sites. Moreover, independent tests show that UbiProber improves the areas under receiver operating characteristic curves by ~15% by using the Combined model. AVAILABILITY: The UbiProber server is freely available on the web at http://bioinfo.ncu.edu.cn/UbiProber.aspx. The software system of UbiProber can be downloaded at the same site. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Proteome-wide analysis of amino acid variations that influence protein lysine acetylation.

Next-generation sequencing (NGS) technologies are yielding ever higher volumes of genetic variation data. Given this large amount of data, it has become both a possibility and a priority to determine what the functional implication of genetic variations is. Considering the essential roles of acetylation in protein functions, it is highly likely that acetylation related genetic variations change protein functions. In this work, we performed a proteome-wide analysis of amino acid variations that could potentially influence protein lysine acetylation characteristics in human variant proteins. Here, we defined the AcetylAAVs as acetylation related amino acid variations that affect acetylation sites or their interacting acetyltransferases, and categorized three types of AcetylAAVs. Using the developed prediction system, named KAcePred, we detected that 50.87% of amino acid variations are potential AcetylAAVs and 12.32% of disease mutations could result in AcetylAAVs. More interestingly, from the statistical analysis, we found that the amino acid variations that directly create new potential lysine acetylation sites have more chance to cause diseases. It can be anticipated that the analysis of AcetylAAVs might be useful to screen important polymorphisms and help to identify the mechanism of genetic diseases. A user-friendly web interface for analysis of AcetylAAVs is now freely available at http://bioinfo.ncu.edu.cn/AcetylAAVs_Home.aspx .

Optimization of reaction conditions towards multiple types of framework isomers and periodic-increased porosity: luminescence properties and selective CO2 adsorption over N2.

Three new metal-organic frameworks (MOFs) were prepared by solvo(hydro)thermolysis and further characterized as framework isomers. The structural transformation from non-porous to porous MOFs and the purity of these products can be modulated by controlling the reaction temperature. The periodic-increased porosity observed was further confirmed by CO2 adsorption isotherms. Owing to the presence of acylamide groups in the pore walls and the flexible nature of the skeleton of these MOFs, highly selective CO2 adsorption over N2 was observed, as well as structure-dependent periodic varieties in luminescence properties.

A novel two-dimensional metal-organic supramolecular framework including π-π stacking and hydrogen-bond interactions.

[µ-N,N'-Bis(pyridin-3-yl)benzene-1,4-dicarboxamide-1:2κ(2)N:N']bis{[N,N'-bis(pyridin-3-yl)benzene-1,4-dicarboxamide-κN]diiodidomercury(II)}, [Hg2I4(C18H14N4O2)3], is an S-shaped dinuclear molecule, composed of two HgI2 units and three N,N'-bis(pyridin-3-yl)benzene-1,4-dicarboxamide (L) ligands. The central L ligand is centrosymmetric and coordinated to two Hg(II) cations via two pyridine N atoms, in a syn-syn conformation. The two terminal L ligands are monodentate, with one uncoordinated pyridine N atom, and each adopts a syn-anti conformation. The HgI2 units show highly distorted tetrahedral (sawhorse) geometry, as the Hg(II) centres lie only 0.34 (2) or 0.32 (2) Šfrom the planes defined by the I and pyridine N atoms. Supramolecular interactions, thermal stability and solid-state luminescence properties were also measured.

Spatial Accessibility and Equity Evaluation of Medical Facilities Based on Improved 2SFCA: A Case Study in Xi'an, China.

Accurate evaluation of the accessibility of medical facilities is a prerequisite for the reasonable allocation of medical resources in a city. The accessibility of medical facilities depends not only on the distance to the supply and demand points, but also on the time spent in the process, and the supply capacity of the supply points. Taking Xi'an City of Shaanxi Province as an example, this paper comprehensively considers the facility supply capacity and introduces the selection probability function based on the two-step floating catchment area (2SFCA) method. In addition, in order to approximate the residents' acceptance of different types of hospitals for long-distance medical treatment in real situations, different levels of search radius were set for the different levels of hospitals, and ArcGIS was used to measure the accessibility and evaluate the spatial layout of medical facilities in the main urban area of Xi'an. The results show that there is a significant difference in the accessibility of medical facilities in the main urban area of Xi'an, and the accessibility tends to decrease gradually from the central city to the periphery. The inequity in the allocation of medical facilities in the main urban area of Xi'an is more obvious, with about 81.64% of people having access to 54.88% of medical resources. The accessibility evaluation model established by the improved 2SFCA method can obtain more accurate and objective evaluation results. This study can provide a reference basis for urban medical facilities' planning and rational spatial layout.

Brain Activation During Working Memory Task in Amnestic Mild Cognitive Impairment Patients and Its Association with Memory and Attention.

BACKGROUND: Amnestic mild cognitive impairment (aMCI) is regarded as a transitional state of Alzheimer's disease, with working memory (WM) impairment. OBJECTIVE: To investigate the brain activity in aMCI patients during WM tasks with the functional near-infrared spectroscopy (fNIRS) technique, as well as explore the association between brain activity and cognitive function in multiple domains. METHODS: This study is a case-control study of 54 aMCI patients and 33 cognitively healthy elderly (NC). All participants underwent neuropsychological assessments. fNIRS was applied to examine the brain activation during the WM task. Multivariable linear regression analysis was applied to evaluate associations between brain activation and cognitive function in multiple domains. RESULTS: Compared to NC subjects, aMCI patients had lower activation in the bilateral prefrontal, parietal, and occipital cortex during the WM task. Additionally, activation in the left prefrontal, bilateral parietal, and occipital cortex during the encoding and maintenance phase was positively associated with memory function. During memory retrieval, higher activity in the left prefrontal, parietal, and occipital cortex were correlated with higher memory scores. Besides, a positive association also formed between attention function and the activation in the left prefrontal, parietal, and occipital cortex during the WM task. CONCLUSION: These findings demonstrated that reduced activation in the prefrontal, parietal and occipital cortex during WM might reflect the risk of cognitive impairment, especially memory and attention function in aMCI patients. Given the brain activation visualization, fNIRS may be a convenient and alternative tool for screening the risk of Alzheimer's disease.

Identify submitochondria and subchloroplast locations with pseudo amino acid composition: approach from the strategy of discrete wavelet transform feature extraction.

It is very challenging and complicated to predict protein locations at the sub-subcellular level. The key to enhancing the prediction quality for protein sub-subcellular locations is to grasp the core features of a protein that can discriminate among proteins with different subcompartment locations. In this study, a different formulation of pseudoamino acid composition by the approach of discrete wavelet transform feature extraction was developed to predict submitochondria and subchloroplast locations. As a result of jackknife cross-validation, with our method, it can efficiently distinguish mitochondrial proteins from chloroplast proteins with total accuracy of 98.8% and obtained a promising total accuracy of 93.38% for predicting submitochondria locations. Especially the predictive accuracy for mitochondrial outer membrane and chloroplast thylakoid lumen were 82.93% and 82.22%, respectively, showing an improvement of 4.88% and 27.22% when other existing methods were compared. The results indicated that the proposed method might be employed as a useful assistant technique for identifying sub-subcellular locations. We have implemented our algorithm as an online service called SubIdent (http://bioinfo.ncu.edu.cn/services.aspx).

PredSulSite: prediction of protein tyrosine sulfation sites with multiple features and analysis.

Tyrosine sulfation is a ubiquitous posttranslational modification that regulates extracellular protein-protein interactions, intracellular protein transportation modulation, and protein proteolytic process. However, identifying tyrosine sulfation sites remains a challenge due to the lability of sulfation sequences. In this study, we developed a method called PredSulSite that incorporates protein secondary structure, physicochemical properties of amino acids, and residue sequence order information based on support vector machine to predict sulfotyrosine sites. Three types of encoding algorithms-secondary structure, grouped weight, and autocorrelation function-were applied to mine features from tyrosine sulfation proteins. The prediction model with multiple features achieved an accuracy of 92.89% in 10-fold cross-validation. Feature analysis showed that the coil structure, acidic amino acids, and residue interactions around the tyrosine sulfation sites all contributed to the sulfation site determination. The detailed feature analysis in this work can help us to understand the sulfation mechanism and provide guidance for the related experimental validation. PredSulSite is available as a community resource at http://www.bioinfo.ncu.edu.cn/inquiries_PredSulSite.aspx.

A method to distinguish between lysine acetylation and lysine methylation from protein sequences.

Lysine acetylation and methylation are two major post-translational modifications of lysine residues. They play vital roles in both biological and pathological processes. Specific lysine residues in H3 histone protein tails appear to be targeted for either acetylation or methylation. Hence it is very challenging to distinguish between acetylated and methylated lysine residues using computational methods. This work presents a method that incorporates protein sequence information, secondary structure and amino acid properties to differentiate acetyl-lysine from methyl-lysine. We apply an encoding scheme based on grouped weight and position weight amino acid composition to extract sequence information and physicochemical properties around lysine sites. The proposed method achieves an accuracy of 93.3% using a jackknife test. Feature analysis demonstrates that the prediction model with multiple features can take full advantage of the supplementary information from different features to improve classification performance and prediction robustness. Analysis of the characteristics of lysine residues which can be either methylated or acetylated shows that they are more similar to methyl-lysine than to acetyl-lysine.

Twisting of the DNA-binding surface by a beta-strand-bearing proline modulates DNA gyrase activity.

DNA gyrase is the only topoisomerase capable of introducing (-) supercoils into relaxed DNA. The C-terminal domain of the gyrase A subunit (GyrA-CTD) and the presence of a gyrase-specific 'GyrA-box' motif within this domain are essential for this unique (-) supercoiling activity by allowing gyrase to wrap DNA around itself. Here we report the crystal structure of Xanthomonas campestris GyrA-CTD and provide the first view of a canonical GyrA-box motif. This structure resembles the GyrA-box-disordered Escherichia coli GyrA-CTD, both adopting a non-planar beta-pinwheel fold composed of six seemingly spirally arranged beta-sheet blades. Interestingly, structural analysis revealed that the non-planar architecture mainly stems from the tilted packing seen between blades 1 and 2, with the packing geometry likely being defined by a conserved and unusual beta-strand-bearing proline. Consequently, the GyrA-box-containing blade 1 is placed at an angled spatial position relative to the other DNA-binding blades, and an abrupt bend is introduced into the otherwise flat DNA-binding surface. Mutagenesis studies support that the proline-induced structural twist contributes directly to gyrase's (-) supercoiling activity. To our knowledge, this is the first demonstration that a beta-strand-bearing proline may impact protein function. Potential relevance of beta-strand-bearing proline to disease phenylketonuria is also noted.

[Effects of sodium tanshinone B on the protein expression of NMDAR1 in rat hippocampal subfields following focal ischemia/reperfusion injury].

UNLABELLED: OBJECTIVE To observe the changing laws of the protein expression of N-methyl D-aspartate receptor (NMDAR) in rat hippocampal subfields following focal ischemia/reperfusion injury, and to study the effects of sodium tanshinone B (STB) on it, thus exploring the possible mechanism of STB for treating cerebral ischemia. METHODS: The rat model of focal cerebral ischemia/reperfusion injury was established using middle cerebral artery occlusion (MCAO) by reversibly inserting a nylon thread. The Wistar rats were randomly divided into the sham-operation group, the I/R model group, and the low, middle, and high dose STB groups. The neural functional disturbance was scored referring to the 5-grade Zea Longa EL standard. The protein expression of NMDAR1 in the ischemic side was detected using immunohistochemical assay. RESULTS: There was statistical difference in the scores of the neural functional disturbance in the middle and high dose STB groups when compared with the model group (P < 0.01). Results of the immunohistochemical assay showed the expression of NMDAR1 in CA1 region was obviously higher in the I/R model group, the low and middle dose STB groups than in the sham-operation group (P < 0.01). The expression of NMDAR1 in CA1 region was obviously lower in the high dose STB group than in the I/R model group (P < 0.01), the low (P < 0.01) and middle dose STB groups (P < 0.05). The expression of NMDAR1 in CA3 region was obviously higher in the low dose STB group and the I/R model group than in the sham-operation group, the middle and high dose STB groups (P < 0.01). The expression of NMDAR1 in CA3 region was obviously higher in the high and middle dose STB groups than in the sham-operation group (P < 0.05). CONCLUSIONS: STB could promote the recovery of neural functions in cerebral ischemia/reperfusion injury rats. STB fought against cerebral ischemia/reperfusion injury by lowering excitable neurotransmitter glumatic acid and reducing the protein expression of NMDAR1.

A Review of the Relationship Between EFL Teachers' Academic Buoyancy, Ambiguity Tolerance, and Hopelessness.

Second/foreign language education has been approved emotionally tense due to its inherent challenges, adversities, complications, and ambiguities. These factors can affect various language teaching and learning domains. Hence, it is critical for EFL teachers to be buoyant and tolerant of ambiguity so that they can teach efficiently and prevent a sense of hopelessness that can damage everything. Although there are investigations on these variables in L2 contexts, their main focus has been on EFL students and teachers' perspectives have been largely ignored. Against this shortcoming, this study aimed to review the definitions, conceptualizations, and research findings related to teachers' academic buoyancy, ambiguity tolerance, and hopelessness. Moreover, practical implications for EFL teachers and teacher trainers are presented to increase their awareness of language teaching challenges and ways to overcome them. Finally, the study provides directions for future research.