The Altitudinal Patterns of Leaf C∶N∶P Stoichiometry Are Regulated by Plant Growth Form,Climate and Soil on Changbai Mountain,China

Understanding the geographic patterns and potential drivers of leaf stoichiometry is critical for modelling the nutrient fluxes of ecosystems and to predict the responses of ecosystems to global changes. This study aimed to explore the altitudinal patterns and potential drivers of leaf C∶N∶P stoichiometry. We measured the concentrations of leaf C, N and P in 175 plant species as well as soil nutrient concentrations along an altitudinal transect (500–2300 m) on the northern slope of Changbai Mountain, China to explore the response of leaf C∶N∶P stoichiometry to plant growth form (PGF), climate and soil. Leaf C, N, P and C∶N∶P ratios showed significant altitudinal trends. In general, leaf C and C∶N∶P ratios increased while leaf N and P decreased with elevation. Woody and herbaceous species showed different responses to altitudinal gradients. Trees had the largest variation in leaf C, C∶N and C∶P ratios, while herbs showed the largest variation in leaf N, P and N∶P ratio. PGF, climate and soil jointly regulated leaf stoichiometry, explaining 17.6% to 52.1% of the variation in the six leaf stoichiometric traits. PGF was more important in explaining leaf stoichiometry variation than soil and climate. Our findings will help to elucidate the altitudinal patterns of leaf stoichiometry and to model ecosystem nutrient cycling.     

Caffeine inactivation of mammalian cells in the S phase of the mitotic cycle due to anomalous replicon initiation during the inhibition of the elongation of replicating DNA

Chinese hamster cells were treated with an inhibitor of DNA synthesis (hydroxyurea or arabinoside-cytesine) in non-toxic concentrations for 20 hours in the presence or absence of caffeine (2 mM). Under these conditions caffeine considerably inactivates the cells. If cells are synchronized by hydroxyurea (0.25 mM) in the S-phase of mitotic cycle, the addition of caffeine kills all the S-phase cells, while gamma-irradiation or novobiocine treatment markedly decreases the sensibilizing effect of caffeine. These findings permit us to conclude that cell inactivation is due to anomalous reinitiation of DNA synthesis stimulated by caffeine in the presence of drugs which inhibit the DNA chain elongation.     

Dopant‐Free,Donor–Acceptor‐Type Polymeric Hole‐Transporting Materials for the Perovskite Solar Cells with Power Conversion Efficiencies over 20%

The rich molecular design of electron donor (D)–acceptor (A) polymers offers many valuable clues to obtain high‐efficiency hole‐transporting materials (HTMs) for use in perovskite solar cells (PVSCs). The fused aromatic or heteroaromatic units can increase the conjugation of the polymer backbone to facilitate electron delocalization, which increases the rigidity of adjacent units to prevent rotational disorder and lower the reorganization energy, leading to improved carrier mobility and optimized film morphology. In this work, fused‐ring ladder‐type indacenodithiophene and indacenodithieno[3,2‐b]thiophene are used as D units, benzodithiophene‐4,8‐dione as the A unit, and thienothiophene as a π‐bridge to form the D–A polymers PBDTT and PBTTT, respectively. Both polymers exhibit favorable properties as HTMs including suitable energy levels, high hole mobility, and excellent film quality. Both dopant‐free HTMs endow n‐i‐p PVSCs with promising performance and stability. A maximum power conversion efficiency of 20.28% is achieved for PBDTT‐based devices, which is among the highest values reported to date.     

Phosphorylation of Mutationally Introduced Tyrosine in the Activation Loop of HER2 Confers Gain-of-Function Activity

Amplification, overexpression, and somatic mutation of the HER2 gene have been reported to play a critical role in tumorigenesis of various cancers. The HER2 H878Y mutation was recently reported in 11% of hepatocellular carcinoma (HCC) patients. However, its functional impact on the HER2 protein and its role in tumorigenesis has not been determined. Here, we show that HER2 H878Y is a gain-of-function mutation. Y878 represents a phosphorylation site, and phospho-Y878 interacts with R898 residue to stabilize the active conformation of HER2, thereby enhancing its kinase activity. H878Y mutant is transforming and the transformed cells are sensitive to HER2 kinase inhibitors. Thus, our study reveals the following novel mechanism underlying the tumorigenic function of the HER2 H878Y mutation: the introduction of a tyrosine residue into the kinase activation loop via mutagenesis modulates the conformation of the kinase, thereby enhancing its activity.     

Congenital Cataract: Prevalence and Surgery Age at Zhongshan Ophthalmic Center (ZOC)

Congenital cataract (CC) is the primary cause of treatable childhood blindness. Population-based assessments of prevalence and surgery age of CC, which are critical for improving management strategies, have been unavailable in China until now. We conducted a hospital-based, cross-sectional study of the hospital charts of CC patients younger than 18 years old from January 2005 to December 2010 at Zhongshan Ophthalmic Center (ZOC) in Guangzhou, China. Residence, gender, age at surgery, hospitalization time, and the presence of other ocular abnormalities were extracted and statistically analyzed in different subgroups. The search identified 1314 patients diagnosed with CC from a total of 136154 hospitalizations, which accounted for 2.39% of all the cataract in-patients and 1.06% of the total in-patients over the six-year study period. Of the identified CC patients, 9.2% had ≥2 hospitalizations due to the necessity of additional surgeries, with a total ratio of boys to girls of 1.75∶1. Based on a subgroup analysis according to age, patients 2–6 years old constituted the highest proportion (29.22%) of all hospitalized CC patients, and those 13–18 years old constituted the lowest proportion (13.47%) of the total number. The average age at surgery was 27.62±23.36 months, but CC patients ≤6 years old (especially ≤6 months old) became increasingly prevalent throughout the 6-year study period. A total of 276 cases (20.93%) of CC were associated with one or more other ocular abnormalities, the highest incidence rates were observed for exotropia (6.24%), nystagmus (6.16%), and refractive error (3.65%). In conclusion, CC patients accounted for 2.39% of all cataract in-patients in a review of 6 years of hospitalization charts from ZOC. The age at the time of surgery decreased over the 6-year study period, which probably reflects the continuing improvement of public awareness of children’s eye care in China.     

The Molecular Engineering of an Anti-Idiotypic Antibody for Pharmacokinetic Analysis of a Fully Human Anti-Infective

Anti-idiotype monoclonal antibodies represent a class of reagents that are potentially optimal for analyzing the pharmacokinetics of fully human, anti-infective antibodies that have been developed as therapeutic candidates. This is particularly important where direct pathogen binding assays are complicated by requirements for biosafety level III or IV for pathogen handling. In this study, we describe the development of a recombinant, anti-idiotype monoclonal antibody termed E1 for the detection of a fully human, serotype-specific, therapeutic antibody candidate for the BSLIII pathogen Dengue virus termed 14c10 hG1. E1 was generated by naïve human Fab phage library panning technology and subsequently engineered as a monoclonal antibody. We show that E1 is highly specific for the fully-folded form of 14c10 hG1 and can be employed for the detection of this antibody in healthy human subjects’ serum by enzyme linked immunosorbent assay. In addition, we show that E1 is capable of blocking the binding of 14c10 hG1 to dengue virus serotype 1. Finally, we show that E1 can detect 14c10 hG1 in mouse serum after the administration of the therapeutic antibody in vivo. E1 represents an important new form of ancillary reagent that can be utilized in the clinical development of a therapeutic human antibody candidate.     

COMSUC: A web server for the identification of consensus molecular subtypes of cancer based on multiple methods and multi-omics data

Extensive amounts of multi-omics data and multiple cancer subtyping methods have been developed rapidly, and generate discrepant clustering results, which poses challenges for cancer molecular subtype research. Thus, the development of methods for the identification of cancer consensus molecular subtypes is essential. The lack of intuitive and easy-to-use analytical tools has posed a barrier. Here, we report on the development of the COnsensus Molecular SUbtype of Cancer (COMSUC) web server. With COMSUC, users can explore consensus molecular subtypes of more than 30 cancers based on eight clustering methods, five types of omics data from public reference datasets or users’ private data, and three consensus clustering methods. The web server provides interactive and modifiable visualization, and publishable output of analysis results. Researchers can also exchange consensus subtype results with collaborators via project IDs. COMSUC is now publicly and freely available with no login requirement at http://comsuc.bioinforai.tech/ (IP address: http://59.110.25.27/). For a video summary of this web server, see S1 Video and S1 File.