The influence of increasing sea surface temperatures (SSTs), in response to greenhouse warming, on wave power (WP) remains uncertain. Here, seasonal relationships between SST anomalies and mean and ...extreme WP over the Indo-Pacific Ocean are examined. Overall, seasonal WP has significantly increased over much of the Pacific, Indian, and Southern Ocean by 1.21-3.10 kW/m dec
over 1979-2019. Contributions from wave characteristics, namely significant wave height (SWH) and peak wave period (PWP), to changes in WP show that SWH contributes most in extra-tropical regions, and PWP most in tropical regions. Further, seasonal relationships between SST anomalies and WP indicate that increases in WP are also seen during strong El Niño years in December-February, and in-phase combinations of El Niño and positive Indian Ocean Dipole (IOD) events during June-August and September-November. Results highlight both long-term increasing SSTs and climate variability roles for inducing large-scale seasonal WP changes throughout the Indo-Pacific.
Neutrophil gelatinase associated lipocalin (NGAL), also known as oncogene 24p3, uterocalin, siderocalin or lipocalin 2, is a 24kDa secreted glycoprotein originally purified from a culture of mouse ...kidney cells infected with simian virus 40 (SV-40). Subsequent investigations have revealed that it is a member of the lipocalin family of proteins that transport small, hydrophobic ligands. Since then, NGAL expression has been reported in several normal tissues where it serves to provide protection against bacterial infection and modulate oxidative stress. Its expression is also dysregulated in several benign and malignant diseases. Its small size, secreted nature and relative stability have led to it being investigated as a diagnostic and prognostic biomarker in numerous diseases including inflammation and cancer. Functional studies, conducted primarily on lipocalin 2 (Lcn2), the mouse homologue of human NGAL have revealed that Lcn2 has a strong affinity for iron complexed to both bacterial siderophores (iron-binding proteins) and certain human proteins like norepinephrine. By sequestering iron-laden siderophores, Lcn2 deprives bacteria of a vital nutrient and thus inhibits their growth (bacteriostatic effect). In malignant cells, its proposed functions range from inhibiting apoptosis (in thyroid cancer cells), invasion and angiogenesis (in pancreatic cancer) to increasing proliferation and metastasis (in breast and colon cancer). Ectopic expression of Lcn2 also promotes BCR-ABL induced chronic myelogenous leukemia in murine models. By transporting iron into and out of the cell, NGAL also regulates iron responsive genes. Further, it stabilizes the proteolytic enzyme matrix metalloprotease-9 (MMP-9) by forming a complex with it, and thereby prevents its autodegradation. The factors regulating NGAL expression are numerous and range from pro-inflammatory cytokines like interleukins, tumor necrosis factor-α and interferons to vitamins like retinoic acid. The purpose of this review article is to examine the expression, structure, regulation and biological role of NGAL and critically assess its potential as a novel diagnostic and prognostic marker in both benign and malignant human diseases.
In recent decades, wave power (WP) energy from the ocean is one of the cleanest renewable energy sources associated with oceanic warming. In Indo-Pacific Ocean, the WP is significantly influenced by ...natural climate variabilities, such as El Niño Southern Oscillation (ENSO), Indian Ocean Dipole (IOD), and Pacific Decadal Oscillation (PDO). In this study, the impact of major climate variability modes on seasonal extreme WP is examined over the period 1979–2019 using ERA5 reanalysis data and the non-stationary generalized extreme value analysis is applied to estimate the climatic extremes. Independent ENSO influence after removing the IOD impact (ENSO|
IOD
) on WP are evident over the northeast and central Pacific during December–February, and March–May, respectively, which subsequently shifts towards the western Pacific in June–August (JJA) and September–November (SON). The ENSO|
PDO
impact on WP exhibits similar yet weaker intensity year round compared to ENSO. Extreme WP responses due to the IOD|
ENSO
include widespread decreases over the tropical and eastern Indian Ocean, with localized increases only over South China and Philippine seas and Bay of Bengal during JJA, and the Arabian Sea during SON. Lastly, for the PDO|
ENSO
, the significant increases in WP are mostly confined to the Pacific, and most prominent in the North Pacific. Composite analysis of different phase combinations of PDO (IOD) with El Niño (La Niña) reveals stronger (weaker) influences year-round. The response patterns in significant wave height, peak wave period, sea surface temperatures, and sea level pressure help to explain the seasonal variations in WP.
Pancreatic cystic lesions (PCLs) are well-known precursors of pancreatic cancer. Their diagnosis can be challenging as their behavior varies from benign to malignant disease. Precise and timely ...management of malignant pancreatic cysts might prevent transformation to pancreatic cancer. However, the current consensus guidelines, which rely on standard imaging features to predict cyst malignancy potential, are conflicting and unclear. This has led to an increased interest in radiomics, a high-throughput extraction of comprehensible data from standard of care images. Radiomics can be used as a diagnostic and prognostic tool in personalized medicine. It utilizes quantitative image analysis to extract features in conjunction with machine learning and artificial intelligence (AI) methods like support vector machines, random forest, and convolutional neural network for feature selection and classification. Selected features can then serve as imaging biomarkers to predict high-risk PCLs. Radiomics studies conducted heretofore on PCLs have shown promising results. This cost-effective approach would help us to differentiate benign PCLs from malignant ones and potentially guide clinical decision-making leading to better utilization of healthcare resources. In this review, we discuss the process of radiomics, its myriad applications such as diagnosis, prognosis, and prediction of therapy response. We also discuss the outcomes of studies involving radiomic analysis of PCLs and pancreatic cancer, and challenges associated with this novel field along with possible solutions. Although these studies highlight the potential benefit of radiomics in the prevention and optimal treatment of pancreatic cancer, further studies are warranted before incorporating radiomics into the clinical decision support system.
•Pancreatic cystic lesions (PCLs) are well known radiographic identifiable precursors of pancreatic ductal adenocarcinoma.•Precise and timely management of malignant pancreatic cysts might prevent transformation to pancreatic cancer.•Radiomics can be used as a diagnostic and decision making tool to differentiate benign PCLs from malignant ones.•We review the radiomics studies done in PCLs, challenges associated with radiomics along with possible solutions.
The purpose of this review based research was to explore whether spirituality can prove useful for the development of executives or not. To realize this, the empirical and theoretical work relating ...to the qualities and traits of spiritual people, revelations from the Holy Scriptures on characteristics of spiritual people, theories and researches on the qualities of effective leaders, effective management skills and appraisal criterions used by various organizations for their executives were reviewed in depth. The review supports adequately that the qualities required for effective managers such as initiative, flexibility, creativity, problem solving abilities, analytical abilities, inter personal skills, wisdom, communication skills, independence, accountability, commitment and learning are the characteristics of spiritual people too. Spiritual people inherit or acquire these qualities due to their ability to experience and connect with their own ultimate formless higher self called the divine particle/ consciousness or spirit through spiritual experience. The findings of this research provide a base to theorize that spirituality which can be learnt and enhanced can prove an effective tool for the transformation and development of executives/ managers. This research proposes inclusion of spiritual orientation of the executives in the development programs and additional weight age to spiritual quotient along with other criterions while selecting people for executive/ managerial posts.
Pancreatic cancer remains a lethal malignancy with poor prognosis owing to therapeutic resistance, frequent recurrence and the absence of treatment strategies that specifically target the tumour and ...its supporting stroma. Deregulated cell-surface proteins drive neoplastic transformations and are envisioned to mediate crosstalk between the tumour and its microenvironment. Emerging studies have elaborated on the role of mucins in diverse biological functions, including enhanced tumorigenicity, invasiveness, metastasis and drug resistance through their characteristic O-linked and N-linked oligosaccharides (glycans), extended structures and unique domains. Multiple mucin domains differentially interact and regulate different components of the tumour microenvironment. This Review discusses: the expression pattern of various mucins in the pancreas under healthy, inflammatory, and cancerous conditions; the context-dependent attributes of mucins that differ under healthy and pathological conditions; the contribution of the tumour microenvironment in pancreatic cancer development and/or progression; diagnostic and/or prognostic efficacy of mucins; and mucin-based therapeutic strategies. Overall, this information should help to delineate the intricacies of pancreatic cancer by exploring the family of mucins, which, through various mechanisms in both tumour cells and the microenvironment, worsen disease outcome.
Differential expression of mucins has been associated with several cancers including colorectal cancer (CRC). In normal physiological conditions, secretory mucin MUC5AC is not expressed in the ...colonic mucosa, whereas its aberrant expression is observed during development of colon cancer and its precursor lesions. To date, the molecular mechanism of MUC5AC in CRC progression and drug resistance remains obscure.
MUC5AC expression was determined in colon tissue microarray by immunohistochemistry. A RNA interference and CRISPR/Cas9-mediated system was used to knockdown/knockout the MUC5AC in CRC cell lines to delineate its role in CRC tumorigenesis using in vitro functional assays and in vivo (sub-cutaneous and colon orthotopic) mouse models. Finally, CRC cell lines and xenograft models were used to identify the mechanism of action of MUC5AC.
Overexpression of MUC5AC is observed in CRC patient tissues and cell lines. MUC5AC expression resulted in enhanced cell invasion and migration, and decreased apoptosis of CRC cells. MUC5AC interacted with CD44 physically, which was accompanied by the activation of Src signaling. Further, the presence of MUC5AC resulted in enhanced tumorigenesis and appearance of metastatic lesions in orthotopic mouse model. Additionally, up-regulation of MUC5AC resulted in resistance to 5-fluorouracil (5-FU) and oxaliplatin, and its knockout increased sensitivity to these drugs. Finally, we observed that up-regulation of MUC5AC conferred resistance to 5-FU through down-regulation of p53 and its target gene p21 and up-regulation of β-catenin and its target genes CD44 and Lgr5.
Our findings suggest that differential expression of secretory mucin MUC5AC results in enhanced tumorigenesis and also confers chemoresistance via CD44/β-catenin/p53/p21 signaling.
More virulent and aggressive races of Puccinia striiformis f. sp. tritici (Pst), the pathogen causing wheat stripe rust, have been spreading around the world since 2000 causing large grain yield ...losses. A better understanding of the genome and genetic diversity of these new Pst races will be useful to develop new strategies to ameliorate these losses. In this study, we generated an improved genome assembly of a post-2000 virulent race from the Western USA designated as PST-130. We implemented a haplotype phasing strategy using the diploid-aware assembler, Falcon-Unzip and new long-read technology from PacBio to phase the two genomes of this dikaryotic organism. The combination of these new technologies resulted in an improved PST-130 assembly with only 151 contigs (85.4 Mb, N50 of 1.44 Mb), and a complementary assembly (haplotigs) with 458 contigs (65.9 Mb, N50 of 0.235 Mb, PRJNA650506). This new assembly improved gene predictions resulting in 228 more predicted complete genes than in the initial Illumina assembly (29,178 contigs, N50 of 5 kb). The alignment of the non-repetitive primary and haplotig contigs revealed and average of 5.22 SNP/kb, with 39.1% showing <2 SNP/kb and 15.9% >10 SNP/kb. This large divergent regions may represent introgressions of chromosome segments from more divergent Pst races in regions where a complete sexual cycle and recombination are possible. We hypothesize that some of the divergent regions in PST-130 may be related to the European "Warrior" race PST-DK0911 because this genome is more similar to PST-130 (3.18 SNP/kb) than to the older European race PST-104E (3.75 SNP/kb). Complete phasing of additional Pst genomes or sequencing individual nuclei will facilitate the tracing of the haploid genomes introduced by the new Pst races into local populations.
Pancreatic cancer is a highly lethal malignancy. Lack of early diagnostic markers makes timely detection of pancreatic cancer a highly challenging endeavor. Exosomes have emerged as information-rich ...cancer specific biomarkers. However, characterization of tumor-specific exosomes has been challenging. This study investigated the proof of principle that exosomes could be used for the detection of pancreatic cancer. Label-free analysis of exosomes purified from normal and pancreatic cancer cell lines was performed using surface enhanced Raman Spectroscopy (SERS) and principal component differential function analysis (PC-DFA), to identify tumor-specific spectral signatures. This method differentiated exosomes originating from pancreatic cancer or normal pancreatic epithelial cell lines with 90% accuracy. The cell line trained PC-DFA algorithm was next applied to SERS spectra of serum-purified exosomes. This method exhibited up to 87% and 90% predictive accuracy for HC and EPC individual samples, respectively. Overall, our study identified utility of SERS spectral signature for deciphering exosomal surface signature.
The present study utilizes exosomes purified from pancreatic cancer and pancreatic epithelial cell lines and surface enhanced Raman spectroscopy (SERS) spectra to train an algorithm by Principle Component-Differential Functional Analysis (PC-DFA). This trained PC-DFA algorithm was subsequently applied to SERS spectra to characterize exosomes as originating from pancreatic patient or healthy patient serum with up to 90% accuracy. Display omitted
Pancreatic cancer (PC) is among foremost causes of cancer related deaths worldwide due to generic symptoms, lack of effective screening strategies and resistance to chemo- and radiotherapies. The ...risk factors associated with PC include several metabolic disorders such as obesity, insulin resistance and type 2 diabetes mellitus (T2DM). Studies have shown that obesity and T2DM are associated with PC pathogenesis; however, their role in PC initiation and development remains obscure.
Several biochemical and physiological factors associated with obesity and/or T2DM including adipokines, inflammatory mediators, and altered microbiome are involved in PC progression and metastasis albeit by different molecular mechanisms. Deep understanding of these factors and causal relationship between factors and altered signaling pathways will facilitate deconvolution of disease complexity as well as lead to development of novel therapies. In the present review, we focuses on the interplay between adipocytokines, gut microbiota, adrenomedullin, hyaluronan, vanin and matrix metalloproteinase affected by metabolic alteration and pancreatic tumor progression.
Metabolic diseases, such as obesity and T2DM, contribute PC development through altered metabolic pathways. Delineating key players in oncogenic development in pancreas due to metabolic disorder could be a beneficial strategy to combat cancers associated with metabolic diseases in particular, PC.
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