Generalized Quasi-Likelihood Ratio Tests for Semiparametric Analysis of Covariance Models in Longitudinal Data

<p>We model generalized longitudinal data from multiple treatment groups by a class of semiparametric analysis of covariance models, which take into account the parametric effects of time dependent covariates and the nonparametric time effects. In these models, the treatment effects are represented by nonparametric functions of time and we propose a generalized quasi-likelihood ratio test procedure to test if these functions are identical. Our estimation procedure is based on profile estimating equations combined with local linear smoothers. We find that the much celebrated Wilks phenomenon which is well established for independent data still holds for longitudinal data if a working independence correlation structure is assumed in the test statistic. However, this property does not hold in general, especially when the working variance function is misspecified. Our empirical study also shows that incorporating correlation into the test statistic does not necessarily improve the power of the test. The proposed methods are illustrated with simulation studies and a real application from opioid dependence treatments. Supplementary materials for this article are available online.</p

High-Resolution Mapping of Amino Acid Residues in DNA–Protein Cross-Links Enabled by Ribonucleotide-Containing DNA

DNA–protein cross-links have broad applications in mapping DNA–protein interactions and provide structural insights into macromolecular structures. However, high-resolution mapping of DNA-interacting amino acid residues with tandem mass spectrometry remains challenging due to difficulties in sample preparation and data analysis. Herein, we developed a method for identifying cross-linking amino residues in DNA–protein cross-links at single amino acid resolution. We leveraged the alkaline lability of ribonucleotides and designed ribonucleotide-containing DNA to produce structurally defined nucleic acid–peptide cross-links under our optimized ribonucleotide cleavage conditions. The structurally defined oligonucleotide–peptide heteroconjugates improved ionization, reduced the database search space, and facilitated the identification of cross-linking residues in peptides. We applied the workflow to identifying abasic (AP) site-interacting residues in human mitochondrial transcription factor A (TFAM)-DNA cross-links. With sub-nmol sample input, we obtained high-quality fragmentation spectra for nucleic acid–peptide cross-links and identified 14 cross-linked lysine residues with the home-built AP_CrosslinkFinder program. Semi-quantification based on integrated peak areas revealed that K186 of TFAM is the major cross-linking residue, consistent with K186 being the closest (to the AP modification) lysine residue in solved TFAM:DNA crystal structures. Additional cross-linking lysine residues (K69, K76, K136, K154) support the dynamic characteristics of TFAM:DNA complexes. Overall, our combined workflow using ribonucleotide as a chemically cleavable DNA modification together with optimized sample preparation and data analysis offers a simple yet powerful approach for mapping cross-linking sites in DNA–protein cross-links. The method is amendable to other chemical or photo-cross-linking systems and can be extended to complex biological samples

Video_2_A new contribution to the raptorial ciliate genus Lacrymaria (Protista: Ciliophora): a brief review and comprehensive descriptions of two new species from Changjiang Estuary.MP4

Ciliates serve as excellent indicators for water quality monitoring. However, their utilization is hindered by various taxonomic confusions. The ciliate genus Lacrymaria Bory de Saint-Vincent, 1824 is commonly found in different aquatic habitats, but its taxonomy has been sparsely investigated using state-of-the-art methods. This study investigated two new Lacrymaria species from Nanhui Wetland, Shanghai, China, using living observation, protargol staining, and molecular phylogeny methods. Lacrymaria songi sp. nov. is 180–340 × 20–25 μm in size and possesses 12–16 somatic kineties, 1 terminal contractile vacuole, 2 macronuclear nodules, and 2 types of rod-shaped extrusomes. Lacrymaria dragescoi sp. nov. is distinguished from its congeners by its cell size of 210–400 × 25–35 μm, 14–17 somatic kineties, 1 terminal contractile vacuole, 1 macronucleus, and 2 types of rod-shaped extrusomes. Phylogenetic analyses based on SSU rRNA gene sequences indicate that Lacrymariidae is monophyletic but Lacrymaria is not. Additionally, a brief review of the genus Lacrymaria is provided in this study. We suggest that L. bulbosa Alekperov, 1984, L. lanceolata Kahl, 1930, and L. ovata Burkovsky, 1970 be removed from the genus and propose Phialina lanceolata nov. comb. and Phialina ovata nov. comb. for the latter two.ZooBank registration: Present work: urn:lsid:zoobank.org:pub:CDFB1EBD-80BD-4533-B391-CEE89F62EDC4 Lacrymaria songi sp. nov.: urn:lsid:zoobank.org:act:417E7C2D-DAEC-4711-90BB-64AB3CD2F7D5 Lacrymaria dragescoi sp. nov.: urn:lsid:zoobank.org:act:8778D6B0-1F2E-473C-BE19-3F685391A40D.</p

Table_1_A new contribution to the raptorial ciliate genus Lacrymaria (Protista: Ciliophora): a brief review and comprehensive descriptions of two new species from Changjiang Estuary.DOCX

Ciliates serve as excellent indicators for water quality monitoring. However, their utilization is hindered by various taxonomic confusions. The ciliate genus Lacrymaria Bory de Saint-Vincent, 1824 is commonly found in different aquatic habitats, but its taxonomy has been sparsely investigated using state-of-the-art methods. This study investigated two new Lacrymaria species from Nanhui Wetland, Shanghai, China, using living observation, protargol staining, and molecular phylogeny methods. Lacrymaria songi sp. nov. is 180–340 × 20–25 μm in size and possesses 12–16 somatic kineties, 1 terminal contractile vacuole, 2 macronuclear nodules, and 2 types of rod-shaped extrusomes. Lacrymaria dragescoi sp. nov. is distinguished from its congeners by its cell size of 210–400 × 25–35 μm, 14–17 somatic kineties, 1 terminal contractile vacuole, 1 macronucleus, and 2 types of rod-shaped extrusomes. Phylogenetic analyses based on SSU rRNA gene sequences indicate that Lacrymariidae is monophyletic but Lacrymaria is not. Additionally, a brief review of the genus Lacrymaria is provided in this study. We suggest that L. bulbosa Alekperov, 1984, L. lanceolata Kahl, 1930, and L. ovata Burkovsky, 1970 be removed from the genus and propose Phialina lanceolata nov. comb. and Phialina ovata nov. comb. for the latter two.ZooBank registration: Present work: urn:lsid:zoobank.org:pub:CDFB1EBD-80BD-4533-B391-CEE89F62EDC4 Lacrymaria songi sp. nov.: urn:lsid:zoobank.org:act:417E7C2D-DAEC-4711-90BB-64AB3CD2F7D5 Lacrymaria dragescoi sp. nov.: urn:lsid:zoobank.org:act:8778D6B0-1F2E-473C-BE19-3F685391A40D.</p

Video_1_A new contribution to the raptorial ciliate genus Lacrymaria (Protista: Ciliophora): a brief review and comprehensive descriptions of two new species from Changjiang Estuary.MP4

Ciliates serve as excellent indicators for water quality monitoring. However, their utilization is hindered by various taxonomic confusions. The ciliate genus Lacrymaria Bory de Saint-Vincent, 1824 is commonly found in different aquatic habitats, but its taxonomy has been sparsely investigated using state-of-the-art methods. This study investigated two new Lacrymaria species from Nanhui Wetland, Shanghai, China, using living observation, protargol staining, and molecular phylogeny methods. Lacrymaria songi sp. nov. is 180–340 × 20–25 μm in size and possesses 12–16 somatic kineties, 1 terminal contractile vacuole, 2 macronuclear nodules, and 2 types of rod-shaped extrusomes. Lacrymaria dragescoi sp. nov. is distinguished from its congeners by its cell size of 210–400 × 25–35 μm, 14–17 somatic kineties, 1 terminal contractile vacuole, 1 macronucleus, and 2 types of rod-shaped extrusomes. Phylogenetic analyses based on SSU rRNA gene sequences indicate that Lacrymariidae is monophyletic but Lacrymaria is not. Additionally, a brief review of the genus Lacrymaria is provided in this study. We suggest that L. bulbosa Alekperov, 1984, L. lanceolata Kahl, 1930, and L. ovata Burkovsky, 1970 be removed from the genus and propose Phialina lanceolata nov. comb. and Phialina ovata nov. comb. for the latter two.ZooBank registration: Present work: urn:lsid:zoobank.org:pub:CDFB1EBD-80BD-4533-B391-CEE89F62EDC4 Lacrymaria songi sp. nov.: urn:lsid:zoobank.org:act:417E7C2D-DAEC-4711-90BB-64AB3CD2F7D5 Lacrymaria dragescoi sp. nov.: urn:lsid:zoobank.org:act:8778D6B0-1F2E-473C-BE19-3F685391A40D.</p

Additional file 1 of Freeprotmap: waiting-free prediction method for protein distance map

Additional file 1: Supplementary No. 1

Table_1_Mental states and personality based on real-time physical activity and facial expression recognition.DOCX

IntroductionTo explore a quick and non-invasive way to measure individual psychological states, this study developed interview-based scales, and multi-modal information was collected from 172 participants.MethodsWe developed the Interview Psychological Symptom Inventory (IPSI) which eventually retained 53 items with nine main factors. All of them performed well in terms of reliability and validity. We used optimized convolutional neural networks and original detection algorithms for the recognition of individual facial expressions and physical activity based on Russell's circumplex model and the five factor model.ResultsWe found that there was a significant correlation between the developed scale and the participants' scores on each factor in the Symptom Checklist-90 (SCL-90) and Big Five Inventory (BFI-2) [r = (−0.257, 0.632), p DiscussionOur research demonstrates that mental health can be monitored and assessed remotely by collecting and analyzing multimodal data from individuals captured by digital tools.</p

First identification of human infection with <i>Erysipelothrix Piscisicarius</i> by metagenomic next-generation sequencing

First identification of human infection with Erysipelothrix Piscisicarius by metagenomic next-generation sequencin

Influence of Asp Isomerization on Trypsin and Trypsin-like Proteolysis

Long-lived proteins (LLPs), although less common than their short-lived counterparts, are increasingly recognized to play important roles in age-related diseases such as Alzheimer’s. In particular, spontaneous chemical modifications can accrue over time that serve as both indicators of and contributors to disrupted autophagy. For example, isomerization in LLPs is common and occurs in the absence of protein turnover while simultaneously interfering with the protein turnover by impeding proteolysis. In addition to the biological implications this creates, isomerization may also interfere with its own analysis. To clarify, bottom-up proteomics experiments rely on protein digestion by proteases, most commonly trypsin, but the extent to which isomerization might interfere with trypsin digestion is unknown. Here, we use a combination of liquid chromatography and mass spectrometry to examine the effect of isomerization on proteolysis by trypsin and chymotrypsin. Isomerized aspartic acid and serine residues (which represent the most common sites of isomerization in LLPs) were placed at various locations relative to the preferred protease cleavage point to evaluate the influence on digestion efficiency. Trypsin was found to be relatively tolerant of isomerization, except when present at the residue immediately C-terminal to Arg/Lys. For chymotrypsin, the influence of isomerization on digestion was less predictable, resulting in long-range interference for some isomer/peptide combinations. Given the trypsin- and chymotrypsin-like behaviors of the 20S proteasome, and to further establish the biological relevance of isomerization in LLPs, substrates with isomerized sites were also tested against proteasomal degradation. Significant disruption of 20S proteolysis was observed, suggesting that if LLPs persist long enough to isomerize, it will be difficult for the cells to digest them

Ketocoumarin-Based Photoinitiators for High-Sensitivity Two-Photon Lithography

Ketocoumarins are attractive and distinct photosensitizers due to their high molar extinction coefficients, high intersystem crossing coefficients, and high photochemical stability. As a classic commercial ketocoumarin-based two-photon initiator, 7-diethylamino-3-thenoylcoumarin (DETC) was widely used in two-photon lithography. However, the large fluorescence quantum yield and low two-photon absorption cross section value greatly limit its application in high-throughput nanofabrication. In this work, a series of DETC derivatives were developed by extending the length of the alkyl chain and integrating different donor and acceptor groups. These ketocoumarin-based initiators, namely, compounds 1–7, were designed, synthesized, and unambiguously characterized. Compared with DETC, these compounds exhibit higher molar extinction coefficient, lower fluorescence quantum yield, higher two-photon absorption cross section, and improved sensitivity in two-photon lithography. Among these molecules, compound 7 with expanded π-electron systems and structures with enhanced intramolecular charge transfer exhibits the best sensitivity in two-photon lithography. With compound 7-based photoresist, many kinds of complex three-dimensional patterns can be fabricated using two-photon lithography at a writing speed of up to 60 mm s–1. The high two-photon initiation sensitivity makes these compounds promising candidates for commercialization and provides a new design concept for the development of new initiators