Downscaled climate change threats to United States freshwater finfish aquaculture.

Climate change threatens food production, yet gaps remain in our understanding of these threats to aquaculture, the fastest growing food production subsector. To build climate-resilient practices and policies we need to quantify and map current and future climate threats to aquaculture. Here, we explore how downscaled climate change [SSP 2 (eq.

Optimization of Neurite Tracing and Further Characterization of Human Monocyte-Derived-Neuronal-like Cells.

Deficits in neuronal structure are consistently associated with neurodevelopmental illnesses such as autism and schizophrenia. Nonetheless, the inability to access neurons from clinical patients has limited the study of early neurostructural changes directly in patients' cells. This obstacle has been circumvented by differentiating stem cells into neurons, although the most used methodologies are time consuming.

Transdifferentiation of Human Circulating Monocytes Into Neuronal-Like Cells in 20 Days and Without Reprograming.

Despite progress, our understanding of psychiatric and neurological illnesses remains poor, at least in part due to the inability to access neurons directly from patients. Currently, there are models available but significant work remains, including the search for a less invasive, inexpensive and rapid method to obtain neuronal-like cells with the capacity to deliver reproducible results. Here, we present a new protocol to transdifferentiate human circulating monocytes into neuronal-like cells in 20 days and without the need for viral insertion or reprograming.

The Fate of Fusions.

The concept of leukocyte-tumor cell fusion as a significant driver of cancer progression has been around a long time, and has garnered growing support over the last several years. The underlying idea seems quite simple and attractive: Fusion of tumor cells (with their inherent genetic instability) with leukocytes, particularly macrophages, could produce hybrids with high invasive capabilities, greatly facilitating their metastatic dissemination, while potentially accelerating tumor cell heterogeneity. While there are a number of attractive features with this story on the surface, the various studies seem to leave us with a conundrum, namely, what is the fate of such fusions?

Tumor-promoting effects of pancreatic cancer cell exosomes on THP-1-derived macrophages.

Pancreatic ductal adenocarcinoma (PDAC) tumor growth is enhanced by tumor-associated macrophages (TAMs), yet the mechanisms by which tumor cells and TAMs communicate are not fully understood. Here we show that exosomes secreted by PDAC cell lines differed in their surface proteins, lipid composition, and efficiency of fusing with THP-1-derived macrophages in vitro. Exosomes from AsPC-1, an ascites-derived human PDAC cell line, were enriched in ICAM-1, which mediated their docking to macrophages through interactions with surface-exposed CD11c on macrophages.

"Stealth dissemination" of macrophage-tumor cell fusions cultured from blood of patients with pancreatic ductal adenocarcinoma.

Here we describe isolation and characterization of macrophage-tumor cell fusions (MTFs) from the blood of pancreatic ductal adenocarcinoma (PDAC) patients. The MTFs were generally aneuploidy, and immunophenotypic characterizations showed that the MTFs express markers characteristic of PDAC and stem cells, as well as M2-polarized macrophages. Single cell RNASeq analyses showed that the MTFs express many transcripts implicated in cancer progression, LINE1 retrotransposons, and very high levels of several long non-coding transcripts involved in metastasis (such as MALAT1).

Effective encapsulation and biological activity of phosphorylated chemotherapeutics in calcium phosphosilicate nanoparticles for the treatment of pancreatic cancer.

Drug resistant cancers like pancreatic ductal adenocarcinoma (PDAC) are difficult to treat, and nanoparticle drug delivery systems can overcome some of the limitations of conventional systemic chemotherapy. In this study, we demonstrate that FdUMP and dFdCMP, the bioactive, phosphorylated metabolites of the chemotherapy drugs 5-FU and gemcitabine, can be encapsulated into calcium phosphosilicate nanoparticles (CPSNPs). The non-phosphorylated drug analogs were not well encapsulated by CPSNPs, suggesting the phosphate modification is essential for effective encapsulation.

A Cholecystokinin B Receptor-Specific DNA Aptamer for Targeting Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinomas (PDACs) constitutively express the G-protein-coupled cholecystokinin B receptor (CCKBR). In this study, we identified DNA aptamers (APs) that bind to the CCKBR and describe their characterization and targeting efficacy. Using dual SELEX selection against "exposed" CCKBR peptides and CCKBR-expressing PDAC cells, a pool of DNA APs was identified.

Histone deacetylase inhibitors as cancer therapeutics.

Cancer cells contain significant alterations in their epigenomic landscape, which several enzyme families reversibly contribute to. One class of epigenetic modifying enzymes is that of histone deacetylases (HDAC), which are receiving considerable scrutiny clinically as a therapeutic target in many cancers. The underlying rationale is that inhibiting HDACs will reverse dysregulated target gene expression by modulating functional histone (or other) acetylation marks.

Biologic Evaluation of Diabetes and Local Recurrence in Non-Small Cell Lung Cancer.

A recent multicenter study led by our institution demonstrated that local recurrence of non-small cell lung cancer (NSCLC) was significantly more frequent in patients with diabetes, raising the possibility of different tumor biology in diabetics. Epithelial-to-mesenchymal transition (EMT) plays a key role in local tumor recurrence and metastasis. In the present study, we investigated differences of tumor microenvironment between patients with and without diabetes by examining expression of EMT markers.

Perioperative circulating tumor cell detection: Current perspectives.

Primary cancer resections and in selected cases surgical metastasectomies significantly improve survival, however many patients develop recurrences. Circulating tumor cells (CTCs) function as an independent marker that could be used in the prognostication of different cancers. Sampling of blood and bone marrow compartments during cancer resections is a unique opportunity to increase individual tumor cell capture efficiency.

Macrophage-tumor cell fusions from peripheral blood of melanoma patients.

Background: While the morbidity and mortality from cancer are largely attributable to its metastatic dissemination, the integral features of the cascade are not well understood. The widely accepted hypothesis is that the primary tumor microenvironment induces the epithelial-to-mesenchymal transition in cancer cells, facilitating their escape into the bloodstream, possibly accompanied by cancer stem cells. An alternative theory for metastasis involves fusion of macrophages with tumor cells (MTFs).

Circulating tumor cell isolation during resection of colorectal cancer lung and liver metastases: a prospective trial with different detection techniques.

Background: Colorectal cancer (CRC) metastasectomy improves survival, however most patient develop recurrences. Circulating tumor cells (CTCs) are an independent prognostic marker in stage IV CRC. We hypothesized that CTCs can be enriched during metastasectomy applying different isolation techniques.

Vagus nerve regulates breast cancer metastasis to the adrenal gland.

Background: Metastasis of breast cancer to adrenal glands may alter neuroendocrine functions which increase the severity of the disease. In this study the role of vagus nerve activity in adrenal metastases was examined.

Materials And Methods: 48 Balb/c mice (n=48) were divided into four groups; control, sham-operated, right vagotomy or left vagotomy.

Biorecognition by DNA oligonucleotides after exposure to photoresists and resist removers.

Combining biological molecules with integrated circuit technology is of considerable interest for next generation sensors and biomedical devices. Current lithographic microfabrication methods, however, were developed for compatibility with silicon technology rather than bioorganic molecules, and consequently it cannot be assumed that biomolecules will remain attached and intact during on-chip processing. Here, we evaluate the effects of three common photoresists (Microposit S1800 series, PMGI SF6, and Megaposit SPR 3012) and two photoresist removers (acetone and 1165 remover) on the ability of surface-immobilized DNA oligonucleotides to selectively recognize their reverse-complementary sequence.

A Speculative Role for Stromal Gastrin Signaling in Development and Dissemination of Pancreatic Ductal Adenocarcinoma.

The peptide growth factor gastrin and its receptor, the G-protein coupled cholecystokinin receptor type B (CCKR), play an integral role in the growth and progression of pancreatic ductal adenocarcinoma (PDAC). Gastrin immunoreactivity is found in the fetal pancreas but its expression is not detected in normal pancreas after birth, except when it is re-expressed in malignant lesions.

Circulating tumor cells in melanoma patients.

Circulating tumor cells (CTCs) are of recognized importance for diagnosis and prognosis of cancer patients. With melanoma, most studies do not show any clear relationship between CTC levels and stage of disease. Here, CTCs were enriched (∼400X) from blood of melanoma patients using a simple centrifugation device (OncoQuick), and 4 melanocyte target RNAs (TYR, MLANA, MITF, and MIF) were quantified using QPCR.

Down-regulation of HtrA1 activates the epithelial-mesenchymal transition and ATM DNA damage response pathways.

Expression of the serine protease HtrA1 is decreased or abrogated in a variety of human primary cancers, and higher levels of HtrA1 expression are directly related to better response to chemotherapeutics. However, the precise mechanisms leading to HtrA1 down regulation during malignant transformation are unclear. To investigate HtrA1 gene regulation in breast cancer, we characterized expression in primary breast tissues and seven human breast epithelial cell lines, including two non-tumorigenic cell lines.

Identification of mammary epithelial cells subject to chronic oxidative stress in mammary epithelium of young women and teenagers living in USA: implication for breast carcinogenesis.

Current knowledge of changes in the mammary epithelium relevant to breast carcinogenesis is limited to when histological changes are already present because of a lack of biomarkers needed to identify where such molecular changes might be ongoing at earlier during the of decades-long latent stages of breast carcinogenesis. Breast reduction tissues from young women and teenagers, representative of USA's high breast cancer incidence population, were studies using immunocytochemistry and targeted PCR arrays in order to learn whether a marker of chronic oxidative-stress [protein adducts of 4-hydroxy-2-nonenal (4HNE)] can identify where molecular changes relevant to carcinogenesis might be taking place prior to any histological changes. 4HNE-immunopositive (4HNE+) mammary epithelial cell-clusters were identified in breast tissue sections from most women and from many teenagers (ages 14-30 y) and, in tissues from women ages 17-27 y with many vs.

Nanoresonator chip-based RNA sensor strategy for detection of circulating tumor cells: response using PCA3 as a prostate cancer marker.

There is widespread interest in circulating tumor cells (CTCs) in blood. Direct detection of CTCs (often < 1/mL) is complicated by a number of factors, but the presence of ∼10(3) to 10(4) copies of target RNA per CTC, coupled with simple enrichments, can greatly increase detection capability. In this study we used resonance frequency shifts induced by mass-amplifying gold nanoparticles to detect a hybridization sandwich bound to functionalized nanowires.

Primer-free aptamer selection using a random DNA library.

Aptamers are highly structured oligonucleotides (DNA or RNA) that can bind to targets with affinities comparable to antibodies (1). They are identified through an in vitro selection process called Systematic Evolution of Ligands by EXponential enrichment (SELEX) to recognize a wide variety of targets, from small molecules to proteins and other macromolecules (2-4). Aptamers have properties that are well suited for in vivo diagnostic and/or therapeutic applications: Besides good specificity and affinity, they are easily synthesized, survive more rigorous processing conditions, they are poorly immunogenic, and their relatively small size can result in facile penetration of tissues.

Primer-free aptamer selection using a random DNA library.

Aptamers are high-affinity oligonucleotides which can be selected from large random libraries by systematic evolution of ligands by exponential enrichment (SELEX) protocols, with affinities and specificities comparable or better than antibodies. The SELEX protocols comprise multiple rounds of selection, each of which require regeneration of bound ligands, which in turn require fixed primer sequences flanking the random library regions. These fixed primer sequences can interfere (with false positives and negatives) with the selection process.

MicroRNAs align with accessible sites in target mRNAs.

The importance of microRNAs (miRs) in control of gene expression is now clearly recognized. While individual microRNAs are thought to target hundreds of disparate mRNAs via imperfect base pairing, little is known about the characteristics of miR target sites. Here we show that the miRs can be aligned with empirically identified accessible sites in a target RNA (Cytokeratin 19, KRT), and that some of the aligned miRs functionally down-regulate KRT expression post-transcriptionally.

Mechanisms of growth inhibition in human papillomavirus positive and negative cervical cancer cells by the chloromethyl ketone protease inhibitor, succinyl-alanine-alanine-proline-phenylalanine chloromethyl ketone.

The chymotrypsin-like serine protease inhibitor, succinyl-alanine-alanine-proline-phenylalanine chloromethyl ketone (AAPF(CMK)), has been shown to have anticarcinogenic activity in a number of model systems and to be relatively selective for a nuclear protease. This inhibitor also has substantial effects on growth of tumorigenic human papillomavirus (HPV)-infected keratinocytes in organotypic raft cultures. Here, we examined the effects of AAPF(CMK) on cell growth, cell-cycle kinetics, apoptosis induction, and DNA synthesis in two human cervical carcinoma cell lines: SiHa cells, which have integrated high-risk HPV-16; and C33a cells, which do not contain HPV DNA.