Fungal adhesion protein guides community behaviors and autoinduction in a paracrine manner

Microbes live mostly in a social community rather than in a planktonic state. Such communities have complex spatiotemporal patterns that require intercellular communication to coordinate gene expression. Here, we demonstrate that Cryptococcus neoformans, a model eukaryotic pathogen, responds to an extracellular signal in constructing its colony morphology. The signal that directs this community behavior is not a molecule of low molecular weight like pheromones or quorum-sensing molecules but a secreted protein. Znf2, a master regulator of morphogenesis in Cryptococcus, is necessary and sufficient for the production of this signal protein. Cfl1, a prominent Znf2-downstream adhesion protein (adhesin), was identified to be responsible for the paracrine communication. Consistent with its role in communication, Cfl1 is highly induced during mating colony differentiation, and some of the Cfl1 proteins undergo shedding and are released from the cell wall. The released Cfl1 is enriched in the extracellular matrix and acts as an autoinduction signal to stimulate neighboring cells to phenocopy Cfl1-expressing cells via the filamentation-signaling pathway. We further demonstrate the importance of an unannotated and yet conserved domain in Cfl1’s signaling activity. Although adhesion proteins have long been considered to be mediators of microbial pathogenicity and the structural components of biofilms, our work presented here provides the direct evidence supporting the signaling activation by microbial adhesion/matrix proteins

MFAP3L activation promotes colorectal cancer cell invasion and metastasis

AbstractAn abundance of microfibril-associated glycoprotein 3-like (MFAP3L) significantly correlates with distant metastasis in colorectal cancer (CRC), although the mechanism has yet to be explained. In this study, we observed that MFAP3L knock-down resulted in reduced CRC cell invasion and hepatic metastasis. We evaluated the cellular location and biochemical functions of MFAP3L and found that this protein was primarily localized in the nucleus of CRC cells and acted as a protein kinase. When EGFR translocated into the nucleus upon stimulation with EGF, MFAP3L was phosphorylated at Tyr287 within its SH2 motif, and the activated form of MFAP3L phosphorylated ERK2 at Thr185 and Tyr187. Moreover, the metastatic behavior of CRC cells in vitro and in vivo could be partially explained by activation of the nuclear ERK pathway through MFAP3L phosphorylation. Hence, we experimentally demonstrated for the first time that MFAP3L likely participates in the nuclear signaling of EGFR and ERK2 and acts as a novel nuclear kinase that impacts CRC metastasis

The Anyang Esophageal Cancer Cohort Study: Study Design, Implementation of Fieldwork, and Use of Computer-Aided Survey System

Background: Human papillomavirus (HPV) has been observed repeatedly in esophageal squamous cell carcinoma (ESCC) tissues. However, the causal relationship between HPV infection and the onset of ESCC remains unknown. A large cohort study focusing on this topic is being carried out in rural Anyang, China. Methodology/Principal Findings: The Anyang Esophageal Cancer Cohort Study (AECCS) is a population-based prospective endoscopic cohort study designed to investigate the association of HPV infection and ESCC. This paper provides information regarding the design and implementation of this study. In particular we describe the recruitment strategies and quality control procedures which have been put into place, and the custom designed computer-aided survey system (CASS) used for this project. This system integrates barcode technology and unique identification numbers, and has been developed to facilitate real-time data management throughout the workflow using a wireless local area network. A total of 8,112 (75.3%) of invited subjects participated in the baseline endoscopic examination; of those invited two years later to take part in the first cycle of follow-up, 91.9 % have complied. Conclusions/Significance: The AECCS study has high potential for evaluating the causal relationship between HPV infection and the occurrence of ESCC. The experience in setting up the AECCS may be beneficial for others planning to initiate simila

Research on a UAV spray system combined with grid atomized droplets

BackgroundsUAVs for crop protection hold significant potential for application in mountainous orchard areas in China. However, certain issues pertaining to UAV spraying need to be addressed for further technological advancement, aimed at enhancing crop protection efficiency and reducing pesticide usage. These challenges include the potential for droplet drift, limited capacity for pesticide solution. Consequently, efforts are required to overcome these limitations and optimize UAV spraying technology.MethodsIn order to balance high deposition and low drift in plant protection UAV spraying, this study proposes a plant protection UAV spraying method. In order to study the operational effects of this spraying method, this study conducted a UAV spray and grid impact test to investigate the effects of different operational parameters on droplet deposition and drift. Meanwhile, a spray model was constructed using machine learning techniques to predict the spraying effect of this method.Results and discussionThis study investigated the droplet deposition rate and downwind drift rate on three types of citrus trees: traditional densely planted trees, dwarf trees, and hedged trees, considering different particle sizes and UAV flight altitudes. Analyzing the effect of increasing the grid on droplet coverage and deposition density for different tree forms. The findings demonstrated a significantly improved droplet deposition rate on dwarf and hedged citrus trees compared to traditional densely planted trees and adopting a fixed-height grid increased droplet coverage and deposition density for both the densely planted and trellised citrus trees, but had the opposite effect on dwarfed citrus trees. When using the grid system. Among the factors examined, the height of the sampling point exhibited the greatest influence on the droplet deposition rate, whereas UAV flight height and droplet particle size had no significant impact. The distance in relation to wind direction had the most substantial effect on droplet drift rate. In terms of predicting droplet drift rate, the BP neural network performed inadequately with a coefficient of determination of 0.88. Conversely, REGRESS, ELM, and RBFNN yielded similar and notably superior results with a coefficient of determination greater than 0.95. Notably, ELM demonstrated the smallest root mean square error

Psoriasin promotes invasion, aggregation and survival of pancreatic cancer cells; association with disease progression

Psoriasin (S100A7) is an 11-kDa small calcium binding protein initially isolated from psoriatic skin lesions. It belongs to the S100 family of proteins which play an important role in a range of cell functions including proliferation, differentiation, migration and apoptosis. Aberrant Psoriasin expression has been implicated in a range of cancers and is often associated with poor prognosis. This study examined the role of Psoriasin on pancreatic cancer cell functions and the implication in progression of the disease. Expression of Psoriasin was determined in a cohort of pancreatic tissues comprised of 126 pancreatic tumours and 114 adjacent non-tumour pancreatic tissues. Knockdown and overexpression of Psoriasin in pancreatic cancer cells was performed using specifically constructed plasmids, which either had anti-Psoriasin ribozyme transgene or the full length human Psoriasin coding sequence. Psoriasin knockdown and overexpression was verified using conventional RT-PCR and qPCR. The effect of manipulating Psoriasin expression on pancreatic cancer cell functions was assessed using several in vitro cell function assays. Local invasive pancreatic cancers extended beyond the pancreas expressed higher levels of Psoriasin transcripts compared with the cancers confined to the pancreas. Primary tumours with distant metastases exhibited a reduced expression of Psoriasin. Psoriasin overexpression cell lines exhibited significantly increased growth and migration compared to control cells. In addition, Psoriasin overexpression resulted in increased pancreatic cancer cell invasion which was associated with upregulation of matrix metalloproteinase-2 (MMP-2) and MMP-9. Overexpression of Psoriasin also promoted aggregation and survival of pancreatic cancer cells when they lost anchorage. Taken together, higher expression of Psoriasin was associated with local invasion in pancreatic cancers. Psoriasin expression is associated with pancreatic cancer cell growth, migration, cell-matrix adhesion, and invasion via regulation of MMPs. As such, the proposed implications of Psoriasin in invasion, disease progression and as a potential therapeutic target warrant further investigation

Reduced kinase D‑interacting substrate of 220 kDa (Kidins220) in pancreatic cancer promotes EGFR/ERK signalling and disease progression

Kidins220 is a transmembrane scaffold protein involved in several types of cancer. The aim of the present study was to examine the role of Kidins220 in tumorigenesis and disease progression of pancreatic cancer. The relevant signalling pathways including EGFR, EMT, and MMP were also investigated. The expression of Kidins220 was examined at the transcript and protein level. The Kidins220 knockdown cell model was established and its influence on cellular functions was determined. Involvement of Kidins220 in tumorigenesis and metastasis was examined in CD1 mice, respectively. The results showed that, reduced Kidin220 expression was associated with tumorigenesis, metastasis, and overall survival of pancreatic cancer. Knockdown of Kidins220 promoted proliferation, colony formation and tumorigenic capacity of pancreatic cancer cells in vitro and in vivo, respectively. Kidins220 regulated pancreatic cancer cell migration through the EGFR/AKT/ERK signalling pathway. Furthermore, enhanced EMT was observed in the pancreatic cancer cell lines with the knockdown of Kidins220, underlying EGFR regulation. Kidins220 also affected cell invasion via MMP1. A reduced expression of Kidins220 was observed in pancreatic cancer, which is associated with disease progression, distant metastasis and poor prognosis. The loss of Kidins220 in pancreatic cancer may contribute to disease progression through the upregulation of EGFR and downstream signalling

Innovations to Attribute Reduction of Covering Decision System Based on Conditional Information Entropy

Traditional rough set theory is mainly used to reduce attributes and extract rules in databases in which attributes are characterised by partitions, which the covering rough set theory, a generalisation of traditional rough set theory, covers. In this article, we posit a method to reduce the attributes of covering decision systems, which are databases incarnated in the form of covers. First, we define different covering decision systems and their attributes’ reductions. Further, we describe the necessity and sufficiency for reductions. Thereafter, we construct a discernible matrix to design algorithms that compute all the reductions of covering decision systems. Finally, the above methods are illustrated using a practical example and the obtained results are contrasted with other results