Epidermal growth factor (EGF) and transforming growth factor (TGFβ1) promote EMT in primary prostate cancer cells via Ras signaling. Inhibitory effects of EGCG on EMT induced matrix metalloproteinase (MMP) activity in prostate cancer cells.

Epithelial to mesenchymal transition (EMT) may be a critical step in prostate cancer progression and metastasis. However, we do not understand the ligands and conditions controlling EMT. We have examined the factors controlling EMT in primary prostate cell lines isolated from human prostate cancer (i.e. IBC-10a and PCa-20a cells). We have shown that a combination of EGF and TGFβ1 (E+T) can promote expression of Vimentin and matrix metalloproteinases (MMP2 and MMP9) during induction of EMT in the primary cell lines. We have found that an intact Ras signaling was essential for E+T induced EMT. We have stably transfected IBC-10a cells with pBABE.ras constructs containing three distinct Ras mutations (i.e. C40, G37 and S35). In cells transfected with C40 and S35, TGFβ1 alone induced MMP2 and MMP9 secretion, whereas, E+T was essential to induce MMP2 and MMP9 secretion in G37 transfected cells (i.e. which activates RalGDS and blocks Akt-1 and MEK signaling). Taken together, the data have shown, for the first time, that E+T activation of Akt-1 and MEK signaling pathways play a key role in EMT. One added goal of the study was to identify potential therapeutic agents which can block EMT. We have found that the green tea extract, Epigallocatechin-3-gallate (EGCG), blocks E+T induced MMP secretion in a dosage dependent manner in both the primary cell lines and malignant PC3ML2 tumor cells. In sum, our work has demonstrated that specific ligands regulate EMT and that a herbal tea extract has potential therapeutic benefit in blocking ligand dependent EMT.M.S., Biomedical Engineering -- Drexel University, 201

Glacial-interglacial seawater isotope change near the Chilean Margin as reflected by δ2H values of C37 alkenones

Stable hydrogen isotopic compositions of long-chain alkenones with 37 carbon atoms (δ2HC37) have been shown to reflect seawater salinity in culture and environmental studies, and this potential sea surface salinity proxy has been applied to several downcore records from different regions. However, previous studies were based solely on a single sediment core and often suggested unlikely large changes in salinity based on existing proxy calibrations. Here we present a new δ2HC37 record, in combination with oxygen isotopes of benthic foraminifera from the same samples, from a sediment core from the Chilean Margin (ODP Site 1235). The observed negative shift in δ2HC37 of 20 ‰ during the last deglaciation was identical to that of a previously published δ2HC37 record from the nearby, but deeper, ODP Site 1234, suggesting a regionally consistent shift in δ2HC37. This change translates into a negative hydrogen isotope shift in the surface seawater of ca. 14 ‰, similar to glacial-interglacial reconstructions based on other δ2HC37 records. The reconstructed bottom seawater oxygen isotope change based on benthic foraminifera during the last deglaciation is approximately -0.8 ‰, in line with previous studies. When translated into hydrogen isotopes of bottom seawater using the modern open-ocean water line, this would suggest a negative change of ca. 5 ‰, smaller than the reconstructed surface seawater shift based on alkenones. The larger change in surface water isotopes suggests that it experienced more freshening during the Holocene than bottom waters, either due to increased freshwater input, reduced evaporation, or a combination of the two

Carboxymethylcellulose hydrogels support central nervous system-derived tumor-cell chemotactic migration: comparison with conventional extracellular matrix macromolecules

The local microenvironment plays an important role in maintaining the dynamics of the extracellular matrix and the cell-extracellular matrix relationship. The extracellular matrix is a complex network of macromolecules with distinct mechanical and biochemical characteristics. Disruptions in extracellular matrix homeostasis are associated with the onset of cancer. The extracellular matrix becomes highly disorganized, and the cell-matrix relationship changes, resulting in altered cell-signaling processes and metastasis. Medulloblastoma is one of the most common malignant pediatric brain tumors in the United States. In order to gain a better understanding of the interplay between cell-extracellular matrix interactions and cell-migratory responses in tumors, eight different matrix macromolecule formulations were investigated using a medulloblastoma-derived cell line: poly-D-lysine, matrigel, laminin, collagen 1, fibronectin, a 10% blend of laminin-collagen 1, a 20% blend of laminin-collagen 1, and a cellulose-derived hydrogel, carboxymethylcellulose. Over time, the average changes in cell morphology were quantified in 2D and 3D, as was migration in the presence and absence of the chemoattractant, epidermal growth factor. Data revealed that carboxymethylcellulose allowed for a cell-extracellular matrix relationship typically believed to be present in tumors, with cells exhibiting a rounded, amoeboid morphology consistent with chemotactic migration, while the other matrices promoted an elongated cell shape as well as both haptotactic and chemotactic motile processes. Therefore, carboxymethylcellulose hydrogels may serve as effective platforms for investigating central nervous system-derived tumor-cell migration in response to soluble factor

Captivity-induced behaviour and spatial learning abilities in an enigmatic, aquifer-dwelling blind eel, Rakthamichthys digressus

We investigated the impact of captive life on behaviour and learning abilities in an enigmatic, aquifer-dwelling blind eel, Rakthamichthys digressus. Of eight major behavioural traits related to exploration and activity in a novel arena, four were significantly altered by life in captivity. While the startle response upon introduction into the arena and overall swimming away from the walls increased after captivity, inactivity exhibited immediately after the startle and the reaction to an external disturbance decreased. We also observed behavioural syndromes between ‘startle responses’ and ‘horizontal wall following’, and between ‘overall activity’ and ‘vertical wall following’; however, these behavioural syndromes were not altered by maintenance in captivity. Interestingly, this blind-eel failed to learn a simple spatial task in a Y-maze apparatus. Captive-associated behavioural changes in R. digressus may influence their survival after reintroduction into natural habitats, and such changes must be taken into account while developing protocols for ex-situ conservation and subsequent release

Evaluating isoprenoidal hydroxylated GDGT-based temperature proxies in surface sediments from the global ocean

Recently developed temperature proxies based on hydroxylated isoprenoid Glycerol Dialkyl Glycerol Tetraethers (OH-isoGDGTs), such as %OH, RI-OH, RI-OH′ and OHC, have shown potential for reconstructing past temperature changes. However, progress has been limited by the lack of a global core-top calibration with ample geographical coverage. Here, we compile an extensive global surface sediment dataset of OH-isoGDGTs as well as regular isoprenoid GDGTs (isoGDGTs), with both data generated at NIOZ (n = 575) and previously published data from other laboratories (n = 297). We find interlaboratory differences for proxy indices that incorporate both OH-isoGDGTs and regular isoGDGTs, indicating that care must be taken in compiling large GDGT datasets from multiple laboratories. Our results confirm a strong temperature signal in the isoGDGT distribution, especially for OH-isoGDGT-0 and non-hydroxylated isoGDGTs, but also reveal that water depth might have an impact on the distribution of OH-isoGDGTs with 1 and 2 cyclopentane moieties. This will affect the RI-OH and RI-OH′ indices, particularly in tropical regions, where OH-isoGDGT-0 occurs at low abundance. We explore new proxy indices that combine the temperature dependence of both isoGDGT and OH-isoGDGT distributions and propose the use of TEX86OH, which includes OH-isoGDGT-0 in the denominator of the TEX86 index. This modification leads to a much higher temperature sensitivity of the index, especially in regions with annual mean sea surface temperatures between 5 and 15 °C. Application of this novel paleothermometer to a polar sediment core suggests that this proxy is likely to result in more reliable temperature reconstructions in polar regions where OH-isoGDGTs are abundant

PANC Study (Pancreatitis: A National Cohort Study): national cohort study examining the first 30 days from presentation of acute pancreatitis in the UK

Abstract Background Acute pancreatitis is a common, yet complex, emergency surgical presentation. Multiple guidelines exist and management can vary significantly. The aim of this first UK, multicentre, prospective cohort study was to assess the variation in management of acute pancreatitis to guide resource planning and optimize treatment. Methods All patients aged greater than or equal to 18 years presenting with acute pancreatitis, as per the Atlanta criteria, from March to April 2021 were eligible for inclusion and followed up for 30 days. Anonymized data were uploaded to a secure electronic database in line with local governance approvals. Results A total of 113 hospitals contributed data on 2580 patients, with an equal sex distribution and a mean age of 57 years. The aetiology was gallstones in 50.6 per cent, with idiopathic the next most common (22.4 per cent). In addition to the 7.6 per cent with a diagnosis of chronic pancreatitis, 20.1 per cent of patients had a previous episode of acute pancreatitis. One in 20 patients were classed as having severe pancreatitis, as per the Atlanta criteria. The overall mortality rate was 2.3 per cent at 30 days, but rose to one in three in the severe group. Predictors of death included male sex, increased age, and frailty; previous acute pancreatitis and gallstones as aetiologies were protective. Smoking status and body mass index did not affect death. Conclusion Most patients presenting with acute pancreatitis have a mild, self-limiting disease. Rates of patients with idiopathic pancreatitis are high. Recurrent attacks of pancreatitis are common, but are likely to have reduced risk of death on subsequent admissions. </jats:sec

Carboxymethylcellulose Hydrogels Support Central Nervous System-Derived Tumor-Cell Chemotactic Migration: Comparison With Conventional Extracellular Matrix Macromolecules

The local microenvironment plays an important role in maintaining the dynamics of the extracellular matrix and the cell-extracellular matrix relationship. The extracellular matrix is a complex network of macromolecules with distinct mechanical and biochemical characteristics. Disruptions in extracellular matrix homeostasis are associated with the onset of cancer. The extracellular matrix becomes highly disorganized, and the cell-matrix relationship changes, resulting in altered cell-signaling processes and metastasis. Medulloblastoma is one of the most common malignant pediatric brain tumors in the United States. In order to gain a better understanding of the interplay between cell-extracellular matrix interactions and cell-migratory responses in tumors, eight different matrix macromolecule formulations were investigated using a medulloblastoma-derived cell line: poly-d-lysine, matrigel, laminin, collagen 1, fibronectin, a 10% blend of laminin-collagen 1, a 20% blend of laminin-collagen 1, and a cellulose-derived hydrogel, carboxymethylcellulose. Over time, the average changes in cell morphology were quantified in 2D and 3D, as was migration in the presence and absence of the chemoattractant, epidermal growth factor. Data revealed that carboxymethylcellulose allowed for a cell-extracellular matrix relationship typically believed to be present in tumors, with cells exhibiting a rounded, amoeboid morphology consistent with chemotactic migration, while the other matrices promoted an elongated cell shape as well as both haptotactic and chemotactic motile processes. Therefore, carboxymethylcellulose hydrogels may serve as effective platforms for investigating central nervous system-derived tumor-cell migration in response to soluble factors. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav

Hydrogen isotopic composition of alkenones and oxygen isotopes of benthic foraminifera from ODP Site 202-1235

Hydrogen isotopic compositions of C37 long chain alkenones (δ2HC37) have been proposed as a proxy for past seawater salinity and applied in several regions. However, previous studies were based solely on a single core and often suggested unlikely large changes in salinity. Here we present a new δ2HC37 record, in combination with oxygen isotopes of benthic foraminifera from the same samples, from a sediment core from the Chilean margin (ODP site 1235). The observed negative shift in δ2HC37 of 20‰ during deglaciation was identical to that of the nearby located, but deeper, ODP core 1234 (Weiss et al., 2019), suggesting a regionally consistent shift in δ2HC37. Here we present an isotope dataset spanning 0.15-94.43 mbsf. The age model of Haettig et al., 2023 covers the last 40.000 years spanning 0.15-49.50 mbfs

Management of AdhogAmlapitta with Ayurveda: A case study

Introduction: Amlapitta mentioned in Ayurveda is one of the common clinical condition of the gastrointestinal system in which Pitta get Vidhagdhm or “Amlam Paka. Causes of Amlapitta especially compromise Ahara Janya Hetu, such as excessive intake of Abhishyandi and Pishtanna, Acidic, Hot substances, Alcohol, Adhyashan, Viruddhashan, Vidahiannapana and intake of food in Ajirna condition. &nbsp;&nbsp;In modern science, Amlapita can be correlated with Gastroesophageal reflux disease (GERD), in which hyperacidity occurs due to excess acid production in the stomach. Aim and objectives: The prime aim of this paper is to study the efficacy of Shamana and Shodhana Chikitsa in Ayurveda in the management of Adhog Amlapitta. Material and method: It is a single case study of 64 years-old male patients who had complaints, e.g., constant Pain in the Epigastric region, Abdominal distension, burning sensation in the throat, chest, and abdomen restlessness. Observations and Results: All clinical features in this patient had reduced significantly by using Shodhana and Shaman Aushadhi recommended by ancient Acharyas in the management of Amlapitta