Symbiosis between Dendrobium catenatum protocorms and Serendipita indica involves the plant hypoxia response pathway.

Mycorrhizae are ubiquitous symbioses established between fungi and plant roots. Orchids, in particular, require compatible mycorrhizal fungi for seed germination and protocorm development. Unlike arbuscular mycorrhizal fungi, which have wide host ranges, orchid mycorrhizal fungi are often highly specific to their host orchids. However, the molecular mechanism of orchid mycorrhizal symbiosis is largely unknown compared to that of arbuscular mycorrhizal and rhizobial symbiosis. Here, we report that an endophytic Sebacinales fungus, Serendipita indica, promotes seed germination and the development of protocorms into plantlets in several epiphytic Epidendroideae orchid species (6 species in 2 genera), including Dendrobium catenatum, a critically endangered orchid with high medicinal value. Although plant-pathogen interaction and high meristematic activity can induce the hypoxic response in plants, it has been unclear whether interactions with beneficial fungi, especially mycorrhizal ones, also involve the hypoxic response. By studying the symbiotic relationship between D. catenatum and S. indica, we determined that hypoxia-responsive genes, such as those encoding alcohol dehydrogenase (ADH), are highly induced in symbiotic D. catenatum protocorms. In situ hybridization assay indicated that the ADH gene is predominantly expressed in the basal mycorrhizal region of symbiotic protocorms. Additionally, the ADH inhibitors puerarin and 4-methylpyrazole both decreased S. indica colonization in D. catenatum protocorms. Thus, our study reveals that S. indica is widely compatible with orchids and that ADH and its related hypoxia-responsive pathway are involved in establishing successful symbiotic relationships in germinating orchids.

Order from chaos in the nucleus.

Although it might appear that chromatin is randomly packed within the nucleus, recent data (Hou et al., 2012, in this issue of Molecular Cell) show that it is organized into defined and functionally important domains marked by preferred intradomain physical contacts, and with boundaries associated with insulator protein occupancy.

MSH6 and PMS2 germ-line pathogenic variants implicated in Lynch syndrome are associated with breast cancer.

PURPOSE: An association of Lynch syndrome (LS) with breast cancer has been long suspected; however, there have been insufficient data to address this question for each of the LS genes individually. METHODS: We conducted a retrospective review of personal and family history in 423 women with pathogenic or likely pathogenic germ-line variants in MLH1 (N = 65), MSH2 (N = 94), MSH6 (N = 140), or PMS2 (N = 124) identified via clinical multigene hereditary cancer testing. Standard incidence ratios (SIRs) of breast cancer were calculated by comparing breast cancer frequencies in our study population with those in the general population (Surveillance, Epidemiology, and End Results 18 data). RESULTS: When evaluating by gene, the age-standardized breast cancer risks for MSH6 (SIR = 2.11; 95% confidence interval (CI), 1.56-2.86) and PMS2 (SIR = 2.92; 95% CI, 2.17-3.92) were associated with a statistically significant risk for breast cancer whereas no association was observed for MLH1 (SIR = 0.87; 95% CI, 0.42-1.83) or MSH2 (SIR = 1.22; 95% CI, 0.72-2.06). CONCLUSION: Our data demonstrate that two LS genes, MSH6 and PMS2, are associated with an increased risk for breast cancer and should be considered when ordering genetic testing for individuals who have a personal and/or family history of breast cancer.

Germline pathogenic variants identified in women with ovarian tumors.

OBJECTIVE: The recognition of genes implicated in ovarian cancer risk beyond BRCA1, BRCA2, and the Lynch syndrome genes has increased the variety of testing options available to providers and patients. We report the frequency of pathogenic variants identified among individuals with ovarian cancer undergoing clinical genetic testing via a multi-gene hereditary cancer panel. METHODS: Genetic testing of up to 32 genes using a hereditary cancer panel was performed on 4439 ovarian cancer cases, and results were analyzed for frequency of pathogenic variants. Statistical comparisons were made using t-tests and Fisher's exact tests. RESULTS: The positive yield was 13.2%. While BRCA1/2 pathogenic variants were most frequent, one third (33.7%) of positive findings were in other homologous recombination genes, and accounted for over 40.0% of findings in endometrioid and clear cell cases. Women with a personal history of breast cancer (22.1%), who reported a family history of ovarian cancer (17.7%), and/or serous histology (14.7%) were most likely to harbor a pathogenic variant. Those with very early onset (<30 years) and late onset (≥70 years) ovarian cancer had low positive yields. CONCLUSIONS: Our study highlights the genetic heterogeneity of ovarian cancer, showing that a large proportion of cases are not due to BRCA1/2 and the Lynch syndrome genes, but still have an identifiable hereditary basis. These findings substantiate the utility of multi-gene panel testing in ovarian cancer care regardless of age at diagnosis, family history, or histologic subtype, providing evidence for testing beyond BRCA1/2 and the Lynch syndrome genes.

Mapping of long-range INS promoter interactions reveals a role for calcium-activated chloride channel ANO1 in insulin secretion.

We used circular chromatin conformation capture (4C) to identify a physical contact in human pancreatic islets between the region near the insulin (INS) promoter and the ANO1 gene, lying 68 Mb away on human chromosome 11, which encodes a Ca(2+)-dependent chloride ion channel. In response to glucose, this contact was strengthened and ANO1 expression increased, whereas inhibition of INS gene transcription by INS promoter targeting siRNA decreased ANO1 expression, revealing a regulatory effect of INS promoter on ANO1 expression. Knockdown of ANO1 expression caused decreased insulin secretion in human islets, establishing a physical proximity-dependent feedback loop involving INS transcription, ANO1 expression, and insulin secretion. To explore a possible role of ANO1 in insulin metabolism, we carried out experiments in Ano1(+/-) mice. We observed reduced serum insulin levels and insulin-to-glucose ratios in high-fat diet-fed Ano1(+/-) mice relative to Ano1(+/+) mice fed the same diet. Our results show that determination of long-range contacts within the nucleus can be used to detect novel and physiologically relevant mechanisms. They also show that networks of long-range physical contacts are important to the regulation of insulin metabolism.

Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing.

PURPOSE: Germ-line testing for panels of cancer genes using next-generation sequencing is becoming more common in clinical care. We report our experience as a clinical laboratory testing both well-established, high-risk cancer genes (e.g., BRCA1/2, MLH1, MSH2) as well as more recently identified cancer genes (e.g., PALB2, BRIP1), many of which have increased but less well-defined penetrance. METHODS: Clinical genetic testing was performed on over 10,000 consecutive cases referred for evaluation of germ-line cancer genes, and results were analyzed for frequency of pathogenic or likely pathogenic variants, and were stratified by testing panel, gene, and clinical history. RESULTS: Overall, a molecular diagnosis was made in 9.0% of patients tested, with the highest yield in the Lynch syndrome/colorectal cancer panel. In patients with breast, ovarian, or colon/stomach cancer, positive yields were 9.7, 13.4, and 14.8%, respectively. Approximately half of the pathogenic variants identified in patients with breast or ovarian cancer were in genes other than BRCA1/2. CONCLUSION: The high frequency of positive results in a wide range of cancer genes, including those of high penetrance and with clinical care guidelines, underscores both the genetic heterogeneity of hereditary cancer and the usefulness of multigene panels over genetic tests of one or two genes.Genet Med 18 8, 823-832.

Microplastic pollution in commercially important edible marine bivalves: A comprehensive review.

Microplastics have become major pollutants in the marine environment and can accumulate in high concentrations, especially in the gut of marine organisms. Unlike other seafood, bivalves are consumed whole, along with their digestive systems, resulting in the transfer of microplastics to humans. Therefore, there is an urgent need to review the status of microplastic pollution in marine bivalves. In this context, this article provides a comprehensive review of the status of microplastic pollution in marine bivalves and the impact of microplastics on the physiology and immunology of marine bivalves. In general, marine bivalves can accumulate high levels of microplastics in a tissue-specific manner. Although microplastic pollution does not cause mortality in bivalves, it can adversely affects bivalves' immunity, byssus production, and reproduction, potentially affecting bivalve populations. This article provides important information that will aid establishing management measures and determining the direction of future research.

Chromatin domains, insulators, and the regulation of gene expression.

The DNA sequence elements called insulators have two basic kinds of properties. Barrier elements block the propagation of heterochromatic structures into adjacent euchromatin. Enhancer blocking elements interfere with interaction between an enhancer and promoter when placed between them. We have dissected a compound insulator element found at the 5' end of the chicken ß-globin locus, which possesses both activities. Barrier insulation is mediated by two kinds of DNA binding proteins: USF1/USF2, a heterodimer which recruits multiple enzyme complexes capable of marking histone on adjacent nucleosomes with 'activating' marks, and Vezf1, which protects against DNA methylation. We have found that the heterochromatic region upstream of the insulator element is maintained in its silent state by a dicer-dependent mechanism, suggesting a mechanism for Vezf1 function in the insulator. Enhancer blocking function in the ß-globin insulator element is conferred by a binding site for CTCF. Consistent with this property, CTCF binding was found some years ago to be essential for imprinted expression at the Igf2/H19 locus. Work in many laboratories has since demonstrated that CTCF helps stabilize long-range interactions in the nucleus. We have recently shown that in the case of the human insulin locus such an interaction, over a distance of ~300kb, can result in stimulation of a target gene which itself is important for insulin secretion. This article is part of a Special Issue entitled: Chromatin in time and space.

Temporal Changes in Litterfall and Nutrient Cycling from 2005-2015 in an Evergreen Broad-Leaved Forest in the Ailao Mountains, China.

The study of litter can provide an important reference for understanding patterns of forest nutrient cycling and sustainable management. Here, we measured litterfall (leaves, branches, etc.) from a wet, evergreen, broad-leaved forest in Ailao Mountains of southwestern China on a monthly basis for 11 years (2005-2015). We measured the total biomass of litter fall as well as its components, and estimated the amount of C, N, P, K, S, Ca, and Mg in the amount of litterfall. We found that: The total litter of evergreen, broadleaved forest in Ailao Mountains from 2005 to 2015 was 7.70-9.46 t/ha, and the output of litterfall differed between years. This provides a safeguard for the soil fertility and biodiversity of the area. The total amount of litterfall and its components showed obvious seasonal variation, with most showing a bimodal pattern (peak from March to May and October to November). The majority of litterfall came from leaves, and the total amount as well as its components were correlated with meteorological factors (wind speed, temperate and precipitation) as well as extreme weather events. We found that among years, the nutrient concentration was sorted as C > Ca > N > K > Mg > S > P. The nutrient concentration in the fallen litter and the amount of nutrients returned showed a decreasing trend, but the decreasing rate was slowed through time. Nutrient cycling was influenced by meteorological factors, such as temperature, precipitation, and wind speed, but the nutrient utilization efficiency is high, the circulation capacity is strong, and the turnover time is short. Our results showed that although there was nutrient loss in this evergreen, broad-leaved forest, the presence of forest litterfall can effectively curb potential ecological problems in the area.

A facile approach to obtain super-hydrophobicity for cotton fiber fabrics.

It is a challenging task to directly apply emulsified silicone oil to the surface of cotton fabric to obtain superhydrophobic properties. In this work, a temperature-responsive microgel was first synthesized and the particle size and distribution of the microgel, thermo-responsiveness, and hydrophobicity of the microgel membrane were investigated. Then, through an emulsifying PMHS/water system with microgels as a Pickering emulsifier, a series of Pickering emulsions were obtained. The results showed that the emulsion had the best stability when the microgel content was 2.14 wt% and the mass ratio of PMHS/water was 3/7. The optical microscopy showed that the oil phase could be uniformly dispersed in aqueous solution, and the liquid phase particle size was about 10-22 µm. And stratification of the Pickering emulsion did not occur when placed at room temperature for over one month. Finally, when the addition of Pickering emulsion is 50 g L-1 and the rolling rate is 80%, through a simple two-dip-two-padding treatment, a cotton fabric can obtain the superhydrophobic effect with a static contact angle of 149.6° at 25 °C and 156.4° at 45 °C. The development of this work provides a simple method to make cotton fabric obtain superhydrophobic effects.

Fast Task Adaptation Based on the Combination of Model-Based and Gradient-Based Meta Learning.

Deep reinforcement learning (DRL) recently has attained remarkable results in various domains, including games, robotics, and recommender system. Nevertheless, an urgent problem in the practical application of DRL is fast adaptation. To this end, this article proposes a new and versatile metalearning approach called fast task adaptation via metalearning (FTAML), which leverages the strengths of the model-based methods and gradient-based metalearning methods for training the initial parameters of the model, such that the model is able to efficiently master unseen tasks with a little amount of data from the tasks. The proposed algorithm makes it possible to separate task optimization and task identification, specifically, the model-based learner helps to identify the pattern of a task, while the gradient-based metalearner is capable of consistently improving the performance with only a few gradient update steps through making use of the task embedding produced by the model-based learner. In addition, the choice of network for the model-based learner in the proposed method is also discussed, and the performance of networks with different depths is explored. Finally, the simulation results on reinforcement learning problems demonstrate that the proposed approach outperforms compared metalearning algorithms and delivers a new state-of-the-art performance on a variety of challenging control tasks.

An Effective Fusing Approach by Combining Connectivity Network Pattern and Temporal-Spatial Analysis for EEG-Based BCI Rehabilitation.

Motor-modality-based brain computer interface (BCI) could promote the neural rehabilitation for stroke patients. Temporal-spatial analysis was commonly used for pattern recognition in this task. This paper introduced a novel connectivity network analysis for EEG-based feature selection. The network features of connectivity pattern not only captured the spatial activities responding to motor task, but also mined the interactive pattern among these cerebral regions. Furthermore, the effective combination between temporal-spatial analysis and network analysis was evaluated for improving the performance of BCI classification (81.7%). And the results demonstrated that it could raise the classification accuracies for most of patients (6 of 7 patients). This proposed method was meaningful for developing the effective BCI training program for stroke rehabilitation.

Aggregation caused quenching to aggregation induced emission transformation: a precise tuning based on BN-doped polycyclic aromatic hydrocarbons toward subcellular organelle specific imaging.

Polycyclic aromatic hydrocarbons (PAHs) with boron-nitrogen (BN) moieties have attracted tremendous interest due to their intriguing electronic and optoelectronic properties. However, most of the BN-fused π-systems reported to date are difficult to modify and exhibit traditional aggregation-caused quenching (ACQ) characteristics. This phenomenon greatly limits their scope of application. Thus, continuing efforts to seek novel, structurally distinct and functionally diverse structures are highly desirable. Herein, we proposed a one-stone-two-birds strategy including simultaneous exploration of reactivity and tuning of the optical and electronic properties for BN-containing π-skeletons through flexible regioselective functionalization engineering. In this way, three novel functionalized BN luminogens (DPA-BN-BFT, MeO-DPA-BN-BFT and DMA-DPA-BN-BFT) with similar structures were obtained. Intriguingly, DPA-BN-BFT, MeO-DPA-BN-BFT and DMA-DPA-BN-BFT exhibit completely different emission behaviors. Fluorogens DPA-BN-BFT and MeO-DPA-BN-BFT exhibit a typical ACQ effect; in sharp contrast, DMA-DPA-BN-BFT possesses a prominent aggregation induced emission (AIE) effect. To the best of our knowledge, this is the first report to integrate ACQ and AIE properties into one BN aromatic backbone with subtle modified structures. Comprehensive analysis of the crystal structure and theoretical calculations reveal that relatively large twisting angles, multiple intermolecular interactions and tight crystal packing modes endow DMA-DPA-BN-BFT with strong AIE behavior. More importantly, cell imaging demonstrated that luminescent materials DPA-BN-BFT and DMA-DPA-BN-BFT can highly selectively and sensitively detect lipid droplets (LDs) in living MCF-7 cells. Overall, this work provides a new viewpoint of the rational design and synthesis of advanced BN-polycyclic aromatics with AIE features and triggers the discovery of new functions and properties of azaborine chemistry.

Evolutionary Multitasking-Based Multiobjective Optimization Algorithm for Channel Selection in Hybrid Brain Computer Interfacing Systems.

Hybrid-modality brain-computer Interfaces (BCIs), which combine motor imagery (MI) bio-signals and steady-state visual evoked potentials (SSVEPs), has attracted wide attention in the research field of neural engineering. The number of channels should be as small as possible for real-life applications. However, most of recent works about channel selection only focus on either the performance of classification task or the effectiveness of device control. Few works conduct channel selection for MI and SSVEP classification tasks simultaneously. In this paper, a multitasking-based multiobjective evolutionary algorithm (EMMOA) was proposed to select appropriate channels for these two classification tasks at the same time. Moreover, a two-stage framework was introduced to balance the number of selected channels and the classification accuracy in the proposed algorithm. The experimental results verified the feasibility of multiobjective optimization methodology for channel selection of hybrid BCI tasks.

An Inter- and Intra-Subject Transfer Calibration Scheme for Improving Feedback Performance of Sensorimotor Rhythm-Based BCI Rehabilitation.

The Brain Computer Interface (BCI) system is a typical neurophysiological application which helps paralyzed patients with human-machine communication. Stroke patients with motor disabilities are able to perform BCI tasks for clinical rehabilitation. This paper proposes an effective scheme of transfer calibration for BCI rehabilitation. The inter- and intra-subject transfer learning approaches can improve the low-precision classification performance for experimental feedback. The results imply that the systematical scheme is positive in increasing the confidence of voluntary training for stroke patients. In addition, it also reduces the time consumption of classifier calibration.

Eto2/MTG16 and MTGR1 are heteromeric corepressors of the TAL1/SCL transcription factor in murine erythroid progenitors.

The TAL1 (or SCL) gene, originally discovered through its involvement by a chromosomal translocation in T-cell acute lymphoblastic leukemia, encodes a basic helix-loop-helix (bHLH) transcription factor essential for hematopoietic and vascular development. To identify its interaction partners, we expressed a tandem epitope-tagged protein in murine erythroleukemia (MEL) cells and characterized affinity-purified Tal1-containing complexes by liquid chromatography-tandem mass spectrometry analysis. In addition to known interacting proteins, two proteins related to the Eight-Twenty-One (ETO) corepressor, Eto2/Mtg16 and Mtgr1, were identified from the peptide fragments analyzed. Tal1 interaction with Eto2 and Mtgr1 was verified by coimmunoprecipitation analysis in Tal1, Eto2-, and Mtgr1-transfected COS-7 cells, MEL cells expressing V5 epitope-tagged Tal1 protein, and non-transfected MEL cells. Mapping analysis with Gal4 fusion proteins demonstrated a requirement for the bHLH domain of Tal1 and TAF110 domain of Eto2 for their interaction, and transient transfection and glutathione S-transferase pull-down analysis showed that Mtgr1 and Eto2 enhanced the other's association with Tal1. Enforced expression of Eto2 in differentiating MEL cells inhibited the promoter of the Protein 4.2 (P4.2) gene, a direct target of TAL1 in erythroid progenitors, and transduction of Eto2 and Mtgr1 augmented Tal1-mediated gene repression. Finally, chromatin immunoprecipitation analysis revealed that Eto2 occupancy of the P4.2 promoter in MEL cells decreased with differentiation, in parallel with a decline in Eto2 protein abundance. These results identify Eto2 and Mtgr1 as authentic interaction partners of Tal1 and suggest they act as heteromeric corepressors of this bHLH transcription factor during erythroid differentiation.

Single-stranded DNA-binding proteins regulate the abundance and function of the LIM-homeodomain transcription factor LHX2 in pituitary cells.

A family of single-stranded DNA-binding proteins (or SSBPs) has been shown to augment the function of LIM-homeodomain (LIM-HD) transcription factors in embryogenesis by interaction with LIM domain-binding protein-1 (LDB1). No DNA-binding complex has been described, however, containing a LIM-HD protein, LDB1, and SSBP, and the mechanism by which SSBPs affect LIM-HD function had not been elucidated. Through use of electrophoretic mobility shift, antibody supershift, and ChIP analyses, we show that an Lhx2-Ldb1-Ssbp3 complex binds a specific element in the Lhx2 target gene Cga (encoding the alpha subunit of glycoprotein hormones) in the alphaT3-1 pituitary cell line. Using overexpression and knockdown approaches, we demonstrate that SSBP3 inhibits Lhx2 and Ldb1 turnover, stimulates assembly of this DNA-binding complex, promotes its recruitment to the Cga promoter, and enhances Cga transcription. These studies provide novel insights into the regulation of pituitary gene expression and LIM-HD function more generally.

Identification of a TAL1 target gene reveals a positive role for the LIM domain-binding protein Ldb1 in erythroid gene expression and differentiation.

The TAL1 (or SCL) gene, originally identified from its involvement by a recurrent chromosomal translocation, encodes a basic helix-loop-helix transcription factor essential for erythropoiesis. Although presumed to regulate transcription, its target genes are largely unknown. We show here that a nuclear complex containing TAL1, its DNA-binding partner E47, zinc finger transcription factor GATA-1, LIM domain protein LMO2, and LIM domain-binding protein Ldb1 transactivates the protein 4.2 (P4.2) gene through two E box GATA elements in its proximal promoter. Binding of this complex to DNA was dependent on the integrity of both E box and GATA sites and was demonstrated to occur on the P4.2 promoter in cells. Maximal transcription in transiently transfected cells required both E box GATA elements and expression of all five components of the complex. This complex was shown, in addition, to be capable of linking in solution double-stranded oligonucleotides corresponding to the two P4.2 E box GATA elements. This DNA-linking activity required Ldb1 and increased with dimethyl sulfoxide-induced differentiation of murine erythroleukemia (MEL) cells. In contrast, enforced expression in MEL cells of dimerization-defective mutant Ldb1, as well as wild-type Ldb1, significantly decreased E box GATA DNA-binding activities, P4.2 promoter activity, and accumulation of P4.2 and beta-globin mRNAs. These studies define a physiologic target for a TAL1- and GATA-1-containing ternary complex and reveal a positive role for Ldb1 in erythroid gene expression and differentiation.

Recruitment of the SWI/SNF protein Brg1 by a multiprotein complex effects transcriptional repression in murine erythroid progenitors.

SWI/SNF complexes are involved in both activation and repression of transcription. While one of two homologous ATPases, Brg1 [Brm (Brahma)-related gene 1] or Brm, is required for their chromatin remodelling function, less is known about how these complexes are recruited to DNA. We recently established that a DNA-binding complex containing TAL1/SCL, E47, GATA-1, LMO2 and Ldb1 stimulates P4.2 (protein 4.2) transcription in erythroid progenitors via two E box-GATA elements in the gene's proximal promoter. We show here that the SWI/SNF protein Brg1 is also associated with this complex and that both the E box and GATA DNA-binding sites in these elements are required for Brg1 recruitment. Further, Brg1 occupancy of the P4.2 promoter decreased with terminal erythroid differentiation in association with increased P4.2 transcription, while enforced expression of Brg1 in murine erythroleukaemia cells reduced P4.2 gene expression. Overexpression of Brg1 was associated with increased occupancy of the P4.2 promoter by the nuclear co-repressor mSin3A and HDAC2 (histone deacetylase 2) and with reduced histone H3 and H4 acetylation. Finally, a specific HDAC inhibitor attenuated Brg1-directed repression of P4.2 promoter activity in transfected cells. These results provide insight into the mechanism by which SWI/SNF proteins are recruited to promoters and suggest that transcription of P4.2, and most likely other genes, is actively repressed until the terminal differentiation of erythroid progenitors.

Generation of 1064 nm pulses accurately synchronized with broadband 794 nm pulses by CW-seeded intracavity non-collinear OPA.

A straightforward all-optical way is demonstrated to synchronize broadband pulses of Ti:sapphire lasers with pulses at 1064 nm, wherein background-free pulses around 1064 nm are generated by non-collinear optical parametric amplification seeded with an intracavity continuous-wave He-Ne laser. The intracavity He-Ne laser provides sufficient seed power to dominate over parametric fluorescence. With an intracavity power of 200 mW, the idler pulse at 1064 nm has the pulse-energy about 6 nJ.