We describe pLink 2, a search engine with higher speed and reliability for proteome-scale identification of cross-linked peptides. With a two-stage open search strategy facilitated by fragment ...indexing, pLink 2 is ~40 times faster than pLink 1 and 3~10 times faster than Kojak. Furthermore, using simulated datasets, synthetic datasets,
N metabolically labeled datasets, and entrapment databases, four analysis methods were designed to evaluate the credibility of ten state-of-the-art search engines. This systematic evaluation shows that pLink 2 outperforms these methods in precision and sensitivity, especially at proteome scales. Lastly, re-analysis of four published proteome-scale cross-linking datasets with pLink 2 required only a fraction of the time used by pLink 1, with up to 27% more cross-linked residue pairs identified. pLink 2 is therefore an efficient and reliable tool for cross-linking mass spectrometry analysis, and the systematic evaluation methods described here will be useful for future software development.
The parenting style will have a subtle influence on children’s peer communication. Previous studies paid more attention to “the influence of mother’s parenting style on children’s empathic ability”. ...Thisstudy adopted a combination of questionnaire method and infant interview method to further explore the influence of different parenting styles on empathic ability between children and peers among 66 toddlers in Y Kindergarten in Fuzhou, Fujian Province. The results showed that authoritative parenting style was positively associated with empathy between toddlers and their peers, while authoritarian, permissive and dismissive parenting styles were negatively associated with empathy between toddlers and their peers. Authoritative parenting style, which is highly responsive and demanding, is associated with children’s ability to empathize with their peers, excluding inevitable factors such as society, family upheaval and physical impairments.
piRNAs (Piwi-interacting small RNAs) engage Piwi Argonautes to silence transposons and promote fertility in animal germlines. Genetic and computational studies have suggested that C. elegans piRNAs ...tolerate mismatched pairing and in principle could target every transcript. Here we employ in vivo cross-linking to identify transcriptome-wide interactions between piRNAs and target RNAs. We show that piRNAs engage all germline mRNAs and that piRNA binding follows microRNA-like pairing rules. Targeting correlates better with binding energy than with piRNA abundance, suggesting that piRNA concentration does not limit targeting. In mRNAs silenced by piRNAs, secondary small RNAs accumulate at the center and ends of piRNA binding sites. In germline-expressed mRNAs, however, targeting by the CSR-1 Argonaute correlates with reduced piRNA binding density and suppression of piRNA-associated secondary small RNAs. Our findings reveal physiologically important and nuanced regulation of individual piRNA targets and provide evidence for a comprehensive post-transcriptional regulatory step in germline gene expression.
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•PIWI CLASH identifies piRNA binding sites transcriptome-wide•piRNAs engage all germline mRNAs via microRNA-like pairing rules•piRNA target sites have distinct 22G-RNA patterns on silenced and expressed mRNAs•Targeting by CSR-1 Argonaute correlates with reduced piRNA binding density
Transcriptome-wide profiling of piRNA targeting rules provides new insights into the interplay between Argonaute pathways and their physiological roles in C. elegans
The interactions between dislocations (dislocations and deformation twins) and boundaries (grain boundaries, twin boundaries and phase interfaces) during deformation at ambient temperatures are ...reviewed with focuses on interaction behaviors, boundary resistances and energies during the interactions, transmission mechanisms, grain size effects and other primary influencing factors. The structure of boundaries, interactions between dislocations and boundaries in coarse-grained, ultrafine-grained and nano-grained metals during deformation at ambient temperatures are summarized, and the advantages and drawbacks of different in-situ techniques are briefly discussed based on experimental and simulation results. The latest studies as well as fundamental concepts are presented with the aim that this paper can serve as a reference in the interactions between dislocations and boundaries during deformation.
•Novel numerical methods for quantifying ruin-related quantities.•Yields deterministic upper and lower bounds with no approximation errors.•Various risk models, such as reflection, non-smooth ...coefficients and finite time.•Further improvements of the quality of bounds are proposed.
We establish a novel numerical quantification method based upon mathematical programming for the ruin-related quantities on collective risk models with fairly general features, such as reflecting, non-homogeneous and multidimensional dynamics with non-smooth coefficients. Rather than seeking approximations with a great deal of computing effort as in the existing numerical approximation methods, the proposed method aims to instantly provide deterministic upper and lower bounds for such quantities as linear combinations of moments or in the explicit polynomial form, without random number generation or sophisticated numerical algorithms. Given that closed-form solutions are rarely available especially in finite-time problems, the upper and lower bounds have great potential to be useful information that can complement approximate solutions obtained from existing numerical methods. We present numerical results throughout to justify the theoretical developments and convergence results so as to illustrate the effectiveness of the proposed method with low computational complexity. We also demonstrate further improvements of the bounds by scaling the problem domain, employing piecewise polynomial test functions and the exponential tempering of the polynomial bases.
Diabetic retinopathy (DR) is one of the serious complications that occurs in diabetic patients that frequently causes blindness. Long noncoding RNAs (lncRNAs) have been associated with DR pathology. ...This study aimed to determine the underlying mechanism of lncRNA maternally expressed gene 3 (MEG3) in association with DNA methyltransferase 1 (DNMT1) in the endothelial-mesenchymal transition (endMT) that occurs in DR. A rat model of DR was induced by streptozotocin (STZ) injection, and a high-glucose (HG)-induced cell model was established by exposing microvascular endothelial cells obtained from retina of rats to HG. Subsequently, MEG3 was overexpressed in rat and cell models to characterize its impact on endMT in DR and the involvement of the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway. Furthermore, the methylation level of MEG3 promoter region was determined with the application of methylation-specific polymerase chain reaction, followed by chromatin immunoprecipitation assay for methyltransferase enrichment. Finally, we examined the regulation of DNMT1 on MEG3 methylation and endMT in the HG-induced cell model. The results obtained revealed downregulated MEG3 expression in DR rat and cell models. Overexpressed MEG3 was shown to suppress endMT in DR rat and cell models through the inhibition of the PI3K/Akt/mTOR signaling pathway. Notably, DNMT1 could promote MEG3 promoter methylation to inhibit MEG3 expression by recruiting methyltransferase, which activated the PI3K/Akt/mTOR signaling pathway to accelerate endMT in DR. These findings further highlighted the inhibitory effect of MEG3 on endMT in DR, thus presenting a novel therapeutic target candidate for DR treatment.
Recent evidence highlights the critical role of effective interference inhibition for optimal memory performance, yet its function in action memory remains relatively underexplored. The current study ...investigated inhibitory processes in action memory during encoding and storage stages. In Experiment 1, 100 participants were divided into high and low cognitive inhibition groups using the Stroop color naming task. They performed either a subject-performed task (SPT) or a verbal task (VT) under varying semantic interference levels to assess the interaction between individual inhibitory abilities and the inhibition processing of action memory during encoding. Results indicated no significant difference in inhibition effects (IF) between high and low inhibition groups in SPT under high semantic interference, while in VT, those with high cognitive inhibition demonstrated significantly greater IF than those with low. Experiment 2, involving 57 participants, employed a point detection task and eye-tracking to explore attentional inhibition mechanisms during action memory storage. Behavioral results showed greater IF for SPT than VT under semantic interference. Eye-tracking revealed higher initial fixation rates and shorter durations for SPT subjects during the early processing stage, and significantly fewer and shorter fixations in the later stage compared to VT subjects. These findings imply stronger inhibitory processing in SPT during both encoding and storage stages under semantic interference, with attentional inhibition of action memories occurring predominantly in the later stage.
Intensive human activities, in particular agricultural and industrial production have led to heavy metal accumulation in the peri-urban agricultural soils of China threatening soil environmental ...quality and agricultural product security. A combination of spatial analysis (SA), Pb isotope ratio analysis (IRA), input fluxes analysis (IFA), and positive matrix factorization (PMF) model was successfully used to assess the status and sources of heavy metals in typical peri-urban agricultural soils from a rapidly developing region of China. Mean concentrations of Cd, As, Hg, Pb, Cu, Zn and Cr in surface soils (0–20 cm) were 0.31, 11.2, 0.08, 35.6, 44.8, 119.0 and 97.0 mg kg−1, respectively, exceeding the local background levels except for Hg. Spatial distribution of heavy metals revealed that agricultural activities have significant influence on heavy metal accumulation in the surface soils. Isotope ratio analysis suggested that fertilization along with atmospheric deposition were the major sources of heavy metal accumulation in the soils. Based on the PMF model, the relative contribution rates of the heavy metals due to fertilizer application, atmospheric deposition, industrial emission, and soil parent materials were 30.8%, 33.0%, 25.4% and 10.8%, respectively, demonstrating that anthropogenic activities had significantly higher contribution than natural sources. This study provides a reliable and robust approach for heavy metals source apportionment in this particular peri-urban area with a clear potential for future application in other regions.
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•Integration of SA, IRA, PMF and IFA consistently apportioned the soil heavy metal sources.•Inputs of heavy metals to soils were mainly allocated to fertilization and atmospheric deposition.•Stable Pb isotope ratio analysis (IRA) supports the assessment of anthropogenic impact on soils.•Regular monitoring and source control should be implemented to prevent soil heavy metals pollution.
Quantitative identification of the sources of heavy metals in agricultural soils will provide useful reference for developing effective policies and standards to control and reduce heavy metal inputs and long-term accumulation.
Precipitation atop the Tibetan Plateau (TP) is delivered by the Indian summer monsoon, the Asian summer monsoon, and weather systems associated with the subtropical westerly jet. Variations in the ...relative importance of the monsoon systems and the westerly jet are hypothesized to have occurred at decadal, millennial and glacial-interglacial scales. However, paleoclimate observations based on explicit climate proxies are still scarce, limiting our understanding of the mechanisms of Holocene climate variability on the Tibetan Plateau (TP). Here we present three independently dated compound specific hydrogen isotope records of sedimentary leaf waxes from lakes on the TP, Bangong Co, Lake Qinghai and Linggo Co. The leaf wax δD records reflect isotopes in precipitation, and we combine these observations with existing isotopic and hydrological data to investigate variations in the influence of the summer monsoon and the westerly jet on the moisture budget of the TP since the Late Pleistocene. δD values of precipitation at all three lakes were relatively positive during the Late Pleistocene indicating a weakened summer monsoon. During the early and mid-Holocene, δD values of precipitation at the three lakes were relatively negative, suggesting the importance of summer monsoon. During the middle to late Holocene, δD values at Bangong Co and Lake Qinghai gradually increased with superimposed episodes of short term of δD variability. However, at Linggo Co in the northern TP, periods of more positive δD values of precipitation correspond to wetter intervals inferred from lake level high stands, and likely reflect variations in moisture associated with the westerly jet. Thus, the δD records at Linggo Co imply the lesser importance of summer monsoon moisture in the hydrologic budget of the northern TP. Collectively, the hydrogen isotope records at these three lakes document millennial and centennial scale variations in the strength of the summer monsoon systems and concurrent changes in the westerly jet. Furthermore, millennial-scale fluctuations in the δD records at the three lakes during the middle to late Holocene suggest episodes of reduced summer monsoonal moisture delivery to these regions, and correspond with intervals of cool sea surface temperatures in the North Atlantic.
•Three independently dated new δD records on the Tibetan Plateau.•Western TP and NE TP were influenced by monsoon during the Holocene.•Northern TP climate was influenced by monsoon and westerlies during the Holocene.•Millennial-scale δD fluctuations related to cool intervals in the North Atlantic.
Piwi-interacting RNAs (piRNAs) are genomically encoded small RNAs that engage Piwi Argonaute proteins to direct mRNA surveillance and transposon silencing. Despite advances in understanding piRNA ...pathways and functions, how the production of piRNA is regulated remains elusive. Here, using a genetic screen, we identify casein kinase II (CK2) as a factor required for piRNA pathway function. We show that CK2 is required for the localization of PRG-1 and for the proper localization of several factors that comprise the 'upstream sequence transcription complex' (USTC), which is required for piRNA transcription. Loss of CK2 impairs piRNA levels suggesting that CK2 promotes USTC function. We identify the USTC component twenty-one-U fouled-up 4 (TOFU-4) as a direct substrate for CK2. Our findings suggest that phosphorylation of TOFU-4 by CK2 promotes the assembly of USTC and piRNA transcription. Notably, during the aging process, CK2 activity declines, resulting in the disassembly of USTC, decreased piRNA production, and defects in piRNA-mediated gene silencing, including transposons silencing. These findings highlight the significance of posttranslational modification in regulating piRNA biogenesis and its implications for the aging process. Overall, our study provides compelling evidence for the involvement of a posttranslational modification mechanism in the regulation of piRNA biogenesis.
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