Developmental regulation of epithelial cell cuboidal-to-squamous transition in Drosophila follicle cells.

Epithelial cells form continuous membranous structures for organ formation, and these cells are classified into three major morphological categories: cuboidal, columnar, and squamous. It is crucial that cells transition between these shapes during the morphogenetic events of organogenesis, yet this process remains poorly understood. All three epithelial cell shapes can be found in the follicular epithelium of Drosophila egg chamber during oogenesis. Squamous cells (SCs) are initially restricted to the anterior terminus in cuboidal shape. They then rapidly become flattened to assume squamous shape by stretching and expansion in 12 â€‹h during midoogenesis. Previously, we reported that Notch signaling activated a zinc-finger transcription factor Broad (Br) at the end of early oogenesis. Here we report that ecdysone and JAK/STAT pathways subsequently converge on Br to serve as an important spatiotemporal regulator of this dramatic morphological change of SCs. The early uniform pattern of Br in the follicular epithelium is directly established by Notch signaling at stage 5 of oogenesis. Later, ecdysone and JAK/STAT signaling activities synergize to suppress Br in SCs from stage 8 to 10a, contributing to proper SC squamous shape. During this process, ecdysone signaling is essential for SC stretching, while JAK/STAT regulates SC clustering and cell fate determination. This study reveals an inhibitory role of ecdysone signaling in suppressing Br in epithelial cell remodeling. In this study we also used single-cell RNA sequencing data to highlight the shift in gene expression which occurs as Br is suppressed and cells become flattened.

Doubling Time of the COVID-19 Epidemic by Province, China.

In China, the doubling time of the coronavirus disease epidemic by province increased during January 20-February 9, 2020. Doubling time estimates ranged from 1.4 (95% CI 1.2-2.0) days for Hunan Province to 3.1 (95% CI 2.1-4.8) days for Xinjiang Province. The estimate for Hubei Province was 2.5 (95% CI 2.4-2.6) days.

Very Short-Term Surface Solar Irradiance Forecasting Based On FengYun-4 Geostationary Satellite.

An algorithm to forecast very short-term (30-180 min) surface solar irradiance using visible and near infrared channels (AGRI) onboard the FengYun-4A (FY-4A) geostationary satellite was constructed and evaluated in this study. The forecasting products include global horizontal irradiance (GHI) and direct normal irradiance (DNI). The forecast results were validated using data from Chengde Meteorological Observatory for four typical months (October 2018, and January, April, and July 2019), representing the four seasons. Particle Image Velocimetry (PIV) was employed to calculate the cloud motion vector (CMV) field from the satellite images. The forecast results were compared with the smart persistence (SP) model. A seasonal study showed that July and April forecasting is more difficult than during October and January. For GHI forecasting, the algorithm outperformed the SP model for all forecasting horizons and all seasons, with the best result being produced in October; the skill score was greater than 20%. For DNI, the algorithm outperformed the SP model in July and October, with skill scores of about 12% and 11%, respectively. Annual performances were evaluated; the results show that the normalized root mean square error (nRMSE) value of GHI for 30-180 min horizon ranged from 26.78% to 36.84%, the skill score reached a maximum of 20.44% at the 30-min horizon, and the skill scores were all above 0 for all time horizons. For DNI, the maximum skill score was 6.62% at the 180-min horizon. Overall, compared with the SP model, the proposed algorithm is more accurate and reliable for GHI forecasting and slightly better for DNI forecasting.

Smart mechanosensing machineries enable migration of vascular smooth muscle cells in atherosclerosis-relevant 3D matrices.

At the early stage of atherosclerosis, neointima is formed due to the migration of vascular smooth muscle cells (VSMCs) from the media to the intima. VSMCs are surrounded by highly adhesive 3D matrices. They take specific strategies to cross various 3D matrices in the media, including heterogeneous collagen and mechanically strong basement membrane. Migration of VSMCs is potentially caused by biomechanical mechanism. Most in vitro studies focus on cell migration on 2D substrates in response to biochemical factors. How the cells move through 3D matrices under the action of mechanosensing machineries remains unexplored. In this review, we propose that several interesting tension-dependent machineries act as "tractor"-posterior myosin II accumulation, and "wrecker"-anterior podosome maintaining, to power VSMCs ahead. VSMCs embedded in 3D matrices may accumulate a minor myosin II isoform, myosin IIB, at the cell rear. Anisotropic myosin IIB distribution creates cell rear, polarizes cell body, pushes the nucleus and reshapes the cell body, and cooperates with a uniformly distributed myosin IIA to propel the cell forward. On the other hand, matrix digestion by podosome further promote the migration when the matrix becomes denser. Actomyosin tension activates Src to induce podosome in soft 3D matrices and retain the podosome integrity to steadily digest the matrix.

E(y)1/TAF9 mediates the transcriptional output of Notch signaling in Drosophila.

Transcriptional activation of Notch signaling targets requires the formation of a ternary complex that involves the intracellular domain of the Notch receptor (NICD), DNA-binding protein Suppressor of Hairless [Su(H), RPBJ in mammals] and coactivator Mastermind (Mam). Here, we report that E(y)1/TAF9, a component of the transcription factor TFIID complex, interacts specifically with the NICD-Su(H)-Mam complex to facilitate the transcriptional output of Notch signaling. We identified E(y)1/TAF9 in a large-scale in vivo RNA interference (RNAi) screen for genes that are involved in a Notch-dependent mitotic-to-endocycle transition in Drosophila follicle cells. Knockdown of e(y)1/TAF9 displayed Notch-mutant-like phenotypes and defects in target gene and activity reporter expression in both the follicle cells and wing imaginal discs. Epistatic analyses in these two tissues indicated that E(y)1/TAF9 functions downstream of Notch cleavage. Biochemical studies in S2 cells demonstrated that E(y)1/TAF9 physically interacts with the transcriptional effectors of Notch signaling Su(H) and NICD. Taken together, our data suggest that the association of the NICD-Su(H)-Mastermind complex with E(y)1/TAF9 in response to Notch activation recruits the transcription initiation complex to induce Notch target genes, coupling Notch signaling with the transcription machinery.

[Recognition of Three Types of Plantation Wood Species with Near Infrared Spectra Coupled with Back-Propagation Network].

In this study, the near infrared spectroscopy coupled with Back-Propagation (BP) network was used for the recognition of three kinds of plantation wood (Eucalyptus urophylla, Pinus massoniana, Populus X euramericana (Dode) Guineir cv. "San Martino" (1-72/58)). The study considered the effects of hidden layer neurons number, spectral pretreatment method and spectral regions on BP model, which are compared with SIMCA model simultaneously. The results showed that, (1) the recognition rate was 97.78% achieved by BP network model with hidden layer neurons number 13 and the spectral region of 780～2 500 nm. (2) BP model with spectral region of 780～2 500 nm was more robust than the other two BP models with spectral regions of 780～1 100 and 1 100～2 500 nm, of which recognition rates were 97.78%, 95.56% and 96.67%, respectively. After the full spectra was pretreated with the first derivative and the second derivative methods, the recognition rates of BP models fell down to 93.33% and 71.11%. However, the recognition rate of BP model rose to 98.89% with the full spectra being pretreated by the multiplicative scatter correction (MSC). (3) Compared with SIMCA models that recognition rates of three spectral regions (780～2 500, 780～1 100 nm, and 1 100～2 500 nm) were 76.67%, 81.11% and 82.22% respectively, BP network work models had higher recognition rates.

Regulation of broad by the Notch pathway affects timing of follicle cell development.

During Drosophila oogenesis, activation of Notch signaling in the follicular epithelium (FE) around stage 6 of oogenesis is essential for entry into the endocycle and a series of other changes such as cell differentiation and migration of subsets of the follicle cells. Notch induces the expression of zinc finger protein Hindsight and suppresses homeodomain protein Cut to regulate the mitotic/endocycle (ME) switch. Here we report that broad (br), encoding a small group of zinc-finger transcription factors resulting from alternative splicing, is a transcriptional target of Notch nuclear effector Suppressor of Hairless (Su(H)). The early pattern of Br in the FE, uniformly expressed except in the polar cells, is established by Notch signaling around stage 6, through the binding of Su(H) to the br early enhancer (brE) region. Mutation of the Su(H) binding site leads to a significant reduction of brE reporter expression in follicle cells undergoing the endocycle. Chromatin immunoprecipitation results further confirm Su(H) binding to the br early enhancer. Consistent with its expression in follicle cells during midoogenesis, loss of br function results in a delayed entry into the endocycle. Our findings suggest an important role of br in the timing of follicle cell development, and its transcriptional regulation by the Notch pathway.

Suboptimal cytoreduction in ovarian carcinoma is associated with molecular pathways characteristic of increased stromal activation.

OBJECTIVE: Suboptimal cytoreductive surgery in advanced epithelial ovarian cancer (EOC) is associated with poor survival but it is unknown if poor outcome is due to the intrinsic biology of unresectable tumors or insufficient surgical effort resulting in residual tumor-sustaining clones. Our objective was to identify the potential molecular pathway(s) and cell type(s) that may be responsible for suboptimal surgical resection. METHODS: By comparing gene expression in optimally and suboptimally cytoreduced patients, we identified a gene network associated with suboptimal cytoreduction and explored the biological processes and cell types associated with this gene network. RESULTS: We show that primary tumors from suboptimally cytoreduced patients express molecular signatures that are typically present in a distinct molecular subtype of EOC characterized by increased stromal activation and lymphovascular invasion. Similar molecular pathways are present in EOC metastases, suggesting that primary tumors in suboptimally cytoreduced patients are biologically similar to metastatic tumors. We demonstrate that the suboptimal cytoreduction network genes are enriched in reactive tumor stroma cells rather than malignant tumor cells. CONCLUSION: Our data suggest that the success of cytoreductive surgery is dictated by tumor biology, such as extensive stromal reaction and increased invasiveness, which may hinder surgical resection and ultimately lead to poor survival.

A large-scale in vivo screen to investigate the roles of human genes in Drosophila melanogaster.

Understanding the signaling pathways in which genes participate is essential for discovering the etiology of diseases in humans. The model organism, Drosophila melanogaster, has been crucial in understanding the signaling pathways in humans, given the evolutionary conservation of a significant number of genes between the two species. Genetic screens using Drosophila are a useful way of testing large number of genes to study their function and roles within signaling pathways. We conducted a large-scale genetic screen to identify which human genes cause an alteration in the morphology of the Drosophila eye. The GMR-Gal4 was employed to activate a single UAS-human gene in the eye tissue. In total, we screened 802 UAS-human gene stocks, corresponding to 787 human protein-coding genes, for the ability to influence eye development. We found that overexpression of 64 human genes were capable of disrupting eye development, as determined by phenotypic changes in eye texture, size, shape, bristle morphology, and ommatidia organization. Subsequent analysis revealed that the fly genome encodes proteins that are homologous to a majority of the 64 human genes, raising the possibility that overexpression of these transgenes altered eye development by altering the activity of evolutionarily conserved developmental signaling pathways. Consistent with this hypothesis, a secondary screen demonstrated that overexpression of fly homologs produced phenotypes that mimicked those produced by overexpression of the human gene. Our screening has identified 64 human genes capable of inducing phenotypes in the fly, offering a foundation for ongoing research aimed at understanding functionally conserved pathways across species.

An Automatic Stage Identification MATLAB Tool to Reveal Notch Expression Pattern in Drosophila Egg Chambers.

Many highly conserved pathways control the development and determine cell fate in organisms. One of these pathways is the Notch signaling pathway that allows for local cell-cell communication. Researchers have found that the timing for when Notch signaling activates the target gene is important for maintaining normal gene expression. Any alterations in the downstream gene expression could cause issues with development or certain diseases. The Drosophila oogenesis is a widely used model in developmental biology for analyzing the Notch pathway. However, determining the stage of oogenesis is difficult and varies depending on individual analyzing it. Here, we provide a MATLAB tool to automatically identify the stage of a Drosophila egg chamber and reveal the Notch expression pattern.

Bioinformatics Tools to Understand Notch.

As a result of the culmination of data, and the fast-paced advancement of new research, all the biological information collected can make it difficult to sort data. This is oftentimes experienced when learning about the human genome. Fortunately, with the advancement of technology, the field of bioinformatics has emerged which has allowed for the creation of a variety of biological databases. These biological databases provide a condensed reservoir of organized information that is easy to use and topic-specific. Here, we provide a list of 39 biological databases that help break down the fundamental details of a gene. This chapter uses the NOTCH1 gene as an example to demonstrate how biological databases can be used to extract gene information. Five sections were created to highlight the major areas needed to build a comprehensive foundation of NOTCH1. The first section lists databases containing basic gene and protein product information. The next section consists of protein interactions and signaling pathway databases which are essential in understanding the biological processes a gene product is involved in. Gene expression and disease databases are the next two sections which are connected since disease results from the aberrant expression of a gene product. The last database section examines model organisms which serve a key role in the study of human genetic diseases. Using these databases, we can elucidate NOTCH1's gene/protein structure, expression, and vital physiological function through the Notch signaling pathway.

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer.

Notch signaling is a highly conserved regulatory pathway involved in many cellular processes. Dysregulation of this signaling pathway often leads to interference with proper development and may even result in initiation or progression of cancers in certain cases. Because this pathway serves complex and versatile functions, it can be studied extensively through many different approaches. Of these, bioinformatics provides an undeniably cost-efficient, approachable, and user-friendly method of study. Bioinformatics is a useful way to extract smaller pieces of information from large-scale datasets. Through the implementation of various bioinformatics approaches, researchers can quickly, reliably, and efficiently interpret these large datasets, yielding insightful applications and scientific discoveries. Here, a protocol is presented for integration of bioinformatics approaches to investigate the role of Notch signaling in ovarian cancer. Furthermore, bioinformatics findings are validated through experimentation.

Analysis of the Temporal Patterning of Notch Downstream Targets during Drosophila melanogaster Egg Chamber Development.

Living organisms require complex signaling interactions and proper regulation of these interactions to influence biological processes. Of these complex networks, one of the most distinguished is the Notch pathway. Dysregulation of this pathway often results in defects during organismal development and can be a causative mechanism for initiation and progression of cancer. Despite previous research entailing the importance of this signaling pathway and the organismal processes that it is involved in, less is known concerning the major Notch downstream targets, especially the onset and sequence in which they are modulated during normal development. As timing of regulation may be linked to many biological processes, we investigated and established a model of temporal patterning of major Notch downstream targets including broad, cut, and hindsight during Drosophila melanogaster egg chamber development. We confirmed the sequential order of Broad upregulation, Hindsight upregulation, and Cut downregulation. In addition, we showed that Notch signaling could be activated at stage 4, one stage earlier than the stage 5, a previously long-held belief. However, our further mitotic marker analysis re-stated that mitotic cycle continues until stage 5. Through our study, we once again validated the effectiveness and reliability of our MATLAB toolbox designed to systematically identify egg chamber stages based on area size, ratio, and additional morphological characteristics.

Doubling Time of the COVID-19 Epidemic by Chinese Province.

COVID-19 epidemic doubling time by Chinese province was increasing from January 20 through February 9, 2020. The harmonic mean of the arithmetic mean doubling time estimates ranged from 1.4 (Hunan, 95% CI, 1.2-2.0) to 3.1 (Xinjiang, 95% CI, 2.1-4.8), with an estimate of 2.5 days (95% CI, 2.4-2.6) for Hubei.

Polyamine Oxidases Play Various Roles in Plant Development and Abiotic Stress Tolerance.

Polyamines not only play roles in plant growth and development, but also adapt to environmental stresses. Polyamines can be oxidized by copper-containing diamine oxidases (CuAOs) and flavin-containing polyamine oxidases (PAOs). Two types of PAOs exist in the plant kingdom; one type catalyzes the back conversion (BC-type) pathway and the other catalyzes the terminal catabolism (TC-type) pathway. The catabolic features and biological functions of plant PAOs have been investigated in various plants in the past years. In this review, we focus on the advance of PAO studies in rice, Arabidopsis, and tomato, and other plant species.

NOTCH2/NOTCH3/DLL3/MAML1/ADAM17 signaling network is associated with ovarian cancer.

Notch signaling is well-known for its role in regulating cell self-renewal and differentiation. Within the cancer research field, it has been identified that dysregulated Notch signaling is involved directly with various types of cancer. Although Notch signaling is generally considered as oncogenic, it sometimes acts as a tumor suppressor, highlighting the complexity of the role of Notch in cancer. A number of studies have associated Notch signaling components with ovarian cancer, but the underlying molecular mechanisms are not well-elucidated. In the present study, the roles of main components of Notch signaling in ovarian cancer were systematically analyzed through large data portals, including Prediction of Clinical Outcomes from Genomic Profiles, Gene Expression across Normal and Tumor tissue, CSIOVDB, Broad Institute Cancer Cell Line Encyclopedia and cBioPortal. Upregulated expression of proteins in the Notch signaling pathway components in ovarian cancer was identified to be generally associated with poor overall and disease-free survival time, and more advanced cancer stages. In addition, Notch components were enriched in ovarian cancer tissues and cell lines. These results led to a proposed neurogenic locus notch homolog protein (NOTCH)2/NOTCH3/Delta-like protein 3/Mastermind-like protein 1/a disintegrin and metalloproteinase domain-containing protein 17 network. Anticancer drugs, developed to target this network, may have high specificity in treating Notch-associated ovarian cancer.

A rare case of stent-assisted coil embolization of coronary artery aneurysm in the left main trigeminal position: Case report.

RATIONALE: Coronary artery aneurysms (CAAs) are uncommon in patients with acute coronary syndrome (ACS). We describe the clinical features and outcomes of stent-assisted coil embolization of a CAA in the trigeminal position. PATIENT CONCERNS: We present a 73-year-old woman with a history of paroxysmal episodes of precordial pain since 1 year. Coronary computed tomography angiography (CTA) revealed an aneurysm (diameter: 9 mm) at the junction of the distal left main coronary artery and the anterior descending branch. Troponin I, CK-MB, creatinine and routine blood investigations were within the normal range. DIAGNOSIS: Coronary artery aneurysm in the left main trigeminal position. INTERVENTIONS: The patient was treated with stent-assisted coil embolization. OUTCOMES: After complete filling of the aneurysm with coil, the microcatheter was withdrawn and the stent released in the descending branch. Two stents were successfully implanted. LESSONS: There is no clear consensus on the optimal therapy for patients with CAAs. Clinicians should be aware of the possible complications of stent-assisted coil embolization of CAA in the main trunk of the coronary artery.

DNA topoisomerase IIα and RAD21 cohesin complex component are predicted as potential therapeutic targets in bladder cancer.

Cancer is essentially a genetic disease. Accumulated gene mutations accelerate genome instability, which eventually leads to uncontrollable growth of the tumor. Bladder cancer is the most common form of urinary tract cancer. This form of cancer has a poor prognosis due to its clinical heterogeneity and molecular diversity. Despite recent scientific advances, the knowledge and treatment of bladder cancer still lags behind that of other types of solid tumor. In the present study, available large data portals and other studies were used to obtain clinically relevant information, and the data were systematically processed to decipher the genes associated with bladder cancer. Genes associated with the survival time of patients with bladder cancer were successfully identified. The genes were enriched in common biological processes and pathways, and upregulated in tumor samples from patients. Among the top genes identified as associated with good or poor survival in bladder cancer, DNA topoisomerase IIα (TOP2α) and RAD21 cohesin complex component (RAD21) were also increased in bladder cancer tissues and cell lines. Therefore, TOP2α and RAD21 could be used as potential therapeutic targets in bladder cancer.

The expansion process of a Stellera chamaejasme population in a degraded alpine meadow of Northwest China.

The expansion of poisonous plants can change vegetation community structures and affect grassland ecosystem service values. Stellera chamaejasme is one of the most important poisonous plants and has rapidly expanded in the arid areas of Northwest China in recent decades. The objective of this study was to elucidate the expansion process and model of an S. chamaejasme population. Therefore, we classified the S. chamaejasme population into five classes based on coverage: 31-40%, 41-50%, 51-60%, 61-70% and 71-80%. We investigated the spatial distribution patterns and the size compositions of S. chamaejasme under different coverages. The results show that the spatial distribution pattern of S. chamaejasme under low coverage (31-40%) at all study scales (0-100 cm) was random; the spatial distribution pattern translated to a clumped distribution from a random distribution at some scales, and the clumped distributions gradually became obvious, with coverage increasing from 41-50% to 61-70%; the spatial distribution tended to be random at all study scales when coverage was increased further (71-80%). However, the spatial distribution patterns were closely related to the size composition of the S. chamaejasme population. In particular, the quantity of older individuals had a significant impact on the variation of the spatial distribution patterns of S. chamaejasme. The spatial distribution pattern varied from a random distribution to a clumped distribution and then returned to a random distribution with increasing coverage (from 31-40% to 71-80%), and this may indicate that the S. chamaejasme patches experienced patch formation and extension and merged with each other.

Effect of simulated microgravity induced PI3K-nos2b signalling on zebrafish cardiovascular plexus network formation.

Local abnormal angiogenesis and cardiovascular system reorganization have been observed in embryos exposed to a simulated microgravity (SM) environment. In this study, changes in key molecular signals and pathways in cardiovascular development have been investigated under microgravity conditions. In particular, the caudal vein plexus (CVP) network, formed by sprouting angiogenesis has been chosen. Zebrafish embryos were exposed to SM using a ground-based microgravity bioreactor for 24 and 36 h. The SM was observed to have no effect on the zebrafish length, tail width and incubation time whereas it was observed to significantly reduce the heart rate frequency and to promote abnormal development of the CVP network in the embryos. Nitric oxide (NO) content demonstrated that the total proteins in zebrafish embryos were significantly higher in SM than in the control group grown under normal conditions. It was then preliminarily determined how NO signals were involved in SM regulated zebrafish CVP network formation. nos2b MO was injected and CVP network evolution was observed in 36 h post fertilization (hpf) under SM condition. The results showed that the CVP network formation was considerably decreased in the nos2b MO treated group. However, this inhibition of the CVP network development was not observed in control MO group, indicating that nos2b is involved in the SM-regulated vascular development process in zebrafish. Moreover, specific phosphoinositide 3-kinase (PI3K) inhibitors such as LY294002 were also tested on zebrafish embryos under SM condition. This treatment significantly inhibited the formation of zebrafish CVP network. Furthermore, overexpression of nos2b partly rescued the LY294002-caused CVP network failure. Therefore, it can be concluded that SM affects zebrafish CVP network remodeling by enhancing angiogenesis. Additionally, the PI3K-nos2b signaling pathway is involved in this process.