Endophilin regulates JNK activation through its interaction with the germinal center kinase-like kinase

The endophilin family of proteins function in clathrin-mediated endocytosis. Here, we have identified and cloned the rat germinal center kinase-like kinase (rGLK), a member of the GCK (germinal center kinase) family of e-Jun N-terminal kinase (JNK) activating enzymes, as a novel endophilin I-binding partner. The interaction occurs both in vitro and in cells and is mediated by the Src homology 3 domain of endophilin I and a region of rGLK containing the endophilin consensus-binding sequence PPRPPPPR. Overlay analysis of rat brain extracts demonstrates that endophilin I is a major Src homology 3 domain-binding partner for rGLK. Overexpression of full-length endophilin I activates rGLK-mediated JNK activation, whereas N- and C-terminal fragments of endophilin I block JNK activation. Thus, endophilin I appears to have a novel function in JNK activation

Environmental burdens of groundwater extraction for irrigation over an inland river basin in Northwest China

Crop production is expected to increase by more than 50% to meet the demand of population growth in China in 2050 (FAO, 2017). Crop production in North China largely depends on irrigation, which is mainly from groundwater in Northwest China. Over-extraction of groundwater is decreasing groundwater levels, and threatening the fragile ecological systems of arid regions. How groundwater levels will change in order to meet the irrigation water requirement in Northwest China has not been extensively investigated to evaluate sustainability of agriculture and the cost to maintain groundwater levels. Here, we examine the dynamic relations between groundwater levels and the amount of irrigation water, by employing the Variable Infiltration Capacity model and an irrigation scheme, for the last three decades in Heihe River basin of China. The results show that on the average about 1.86 m decline of groundwater is attributable to the irrigation water consumption for the farmland area in Heihe River over the past three decades. In the scenario of ceasing irrigation activities, the groundwater level will be prevented to further decline about 3.06±0.4m under the future climate scenarios till 2050, but at the cost of crop production valued 64.2±8.4 billion CNY. Effective water-saving measures and strategies are expected to adopt to maintain both groundwater levels and agricultural productivity for the coming decades

Robust Fine Registration of Multisensor Remote Sensing Images Based on Enhanced Subpixel Phase Correlation

Automatic fine registration of multisensor images plays an essential role in many remote sensing applications. However, it is always a challenging task due to significant radiometric and textural differences. In this paper, an enhanced subpixel phase correlation method is proposed, which embeds phase congruency-based structural representation, L1-norm-based rank-one matrix approximation with adaptive masking, and stable robust model fitting into the conventional calculation framework in the frequency domain. The aim is to improve the accuracy and robustness of subpixel translation estimation in practical cases. In addition, template matching using the enhanced subpixel phase correlation is integrated to realize reliable fine registration, which is able to extract a sufficient number of well-distributed and high-accuracy tie points and reduce the local misalignment for coarsely coregistered multisensor remote sensing images. Experiments undertaken with images from different satellites and sensors were carried out in two parts: tie point matching and fine registration. The results of qualitative analysis and quantitative comparison with the state-of-the-art area-based and feature-based matching methods demonstrate the effectiveness and reliability of the proposed method for multisensor matching and registration.TU Berlin, Open-Access-Mittel – 202

A novel vaccine candidate based on chimeric virus-like particle displaying multiple conserved epitope peptides induced neutralizing antibodies against EBV infection.

Epstein-Barr virus (EBV) is the causative pathogen for infectious mononucleosis and many kinds of malignancies including several lymphomas such as Hodgkin\u27s lymphoma, Burkitt\u27s lymphoma and NK/T cell lymphoma as well as carcinomas such as nasopharyngeal carcinoma (NPC) and EBV-associated gastric carcinoma (EBV-GC). However, to date no available prophylactic vaccine was launched to the market for clinical use

Ligand-Dependent TrkA Activity in Brain Differentially Affects Spatial Learning and Long-Term Memory

ABSTRACT In the central nervous system, the nerve growth factor (NGF) receptor TrkA is expressed primarily in cholinergic neurons that are implicated in spatial learning and memory, whereas the NGF receptor p75 NTR is expressed in many neuronal populations and glia. We asked whether selective TrkA activation may have a different impact on learning, short-term memory, and long-term memory. We also asked whether TrkA activation might affect cognition differently in wild-type mice versus mice with cognitive deficits due to transgenic overexpression of mutant amyloid-precursor protein (APP mice). Mice were treated with wild-type NGF (a ligand of TrkA and p75 NTR ) or with selective pharmacological agonists of TrkA that do not bind to p75 NTR . In APP mice, the selective TrkA agonists significantly improved learning and short-term memory. These improvements are associated with a reduction of soluble A␤ levels in the cortex and AKT activation in the cortex and hippocampus. However, this improved phenotype did not translate into improved long-term memory. In normal wild-type mice, none of the treatments affected learning or short-term memory, but a TrkA-selective agonist caused persistent deficits in long-term memory. The deficit in wild-type mice was associated temporally, in the hippocampus, with increased AKT activity, increased brain-derived neurotrophic factor precursor, increased neurotrophin receptor homolog-2 (p75-related protein), and long-term depression. Together, these data indicate that selective TrkA activation affects cognition but does so differently in impaired APP mice versus normal wild-type mice. Understanding mechanisms that govern learning and memory is important for better treatment of cognitive disorders

Antifungal susceptibility profiles and drug resistance mechanisms of clinical Candida duobushaemulonii isolates from China

Candida duobushaemulonii, type II Candida haemulonii complex, is closely related to Candida auris and capable of causing invasive and non-invasive infections in humans. Eleven strains of C. duobushaemulonii were collected from China Hospital Invasive Fungal Surveillance Net (CHIF-NET) and identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF), VITEK 2 Yeast Identification Card (YST), and internal transcribed spacer (ITS) sequencing. Whole genome sequencing of C. duobushaemulonii was done to determine their genotypes. Furthermore, C. duobushaemulonii strains were tested by Sensititre YeastOne™ and Clinical and Laboratory Institute (CLSI) broth microdilution panel for antifungal susceptibility. Three C. duobushaemulonii could not be identified by VITEK 2. All 11 isolates had high minimum inhibitory concentrations (MICs) to amphotericin B more than 2 μg/ml. One isolate showed a high MIC value of ≥64 μg/ml to 5-flucytosine. All isolates were wild type (WT) for triazoles and echinocandins. FUR1 variation may result in C. duobushaemulonii with high MIC to 5-flucytosine. Candida duobushaemulonii mainly infects patients with weakened immunity, and the amphotericin B resistance of these isolates might represent a challenge to clinical treatment

Prevalence, clinical characteristics, and long-term outcomes of new diabetes diagnosis in elderly patients undergoing percutaneous coronary intervention

Previous studies have reported associations between newly diagnosed diabetes and poor outcomes after percutaneous coronary intervention (PCI), but there is limited data focusing on elderly patients (age ≥ 65). This study aimed to analyze the prevalence and clinical implications of newly diagnosed diabetes in elderly patients who underwent PCI. From 2004 to 2021, a total of 2456 elderly patients who underwent invasive PCI at Korea University Guro Hospital were prospectively enrolled and followed up for a median of five years. The primary endpoint was five-year major adverse cardiovascular events (MACE). Cox regression was used to evaluate whether newly diagnosed diabetes impacted on long-term clinical outcomes. Newly diagnosed diabetes was presented in approximately 8.1% to 10.9% of elderly patients who underwent PCI. Those who had a new diagnosis of diabetes had a higher risk of MACE than previously known diabetes (25.28% vs. 19.15%, p = 0.039). After adjusting for significant factors, newly diagnosed diabetes remained an independent predictor of MACE (HR [hazard ratio] 1.64, 95% confidence interval [CI] 1.24-2.17, p < 0.001), cardiac death (HR 2.15, 95% CI 1.29-3.59, p = 0.003) and repeat revascularization (HR 1.52, 95% CI 1.09-2.11, p = 0.013), but not for non-fatal myocardial infarction (HR 1.66, 95% CI 0.94-2.12, p = 0.081). Newly diagnosed diabetes was associated with an increased risk of 5-year MACE compared with non-diabetes and previously diagnosed diabetes in elderly patients underwent PCI. More attention should be given to those elderly newly diagnosed diabetes population

NOXA-Induced Alterations in the Bax/Smac Axis Enhance Sensitivity of Ovarian Cancer Cells to Cisplatin

Ovarian cancer is the most common cause of death from gynecologic malignancy. Deregulation of p53 and/or p73-associated apoptotic pathways contribute to the platinum-based resistance in ovarian cancer. NOXA, a pro-apoptotic BH3-only protein, is identified as a transcription target of p53 and/or p73. In this study, we found that genetic variants of Bcl-2 proteins exist among cisplatin-sensitive and -resistant ovarian cancer cells, and the responses of NOXA and Bax to cisplatin are regulated mainly by p53. We further evaluated the effect of NOXA on cisplatin. NOXA induced apoptosis and sensitized A2780s and SKOV3 cells to cisplatin in vitro and in vivo. The effects were mediated by elevated Bax expression, enhanced caspase activation, release of Cyt C and Smac into the cytosol. Furthermore, gene silencing of Bax or Smac significantly attenuated NOXA and/or cisplatin-induced apoptosis in chemosensitive A2780s cells, whereas overexpression of Bax or addition of Smac-N7 peptide significantly increased NOXA and/or cisplatin-induced apoptosis in chemoresistant SKOV3 cells. To our knowledge, these data suggest a new mechanism by which NOXA chemosensitized ovarian cancer cells to cisplatin by inducing alterations in the Bax/Smac axis. Taken together, our findings show that NOXA is potentially useful as a chemosensitizer in ovarian cancer therapy

A review on the two-phase pressure drop characteristics in helically coiled tubes

Due to their compact design, ease of manufacture and enhanced heat transfer and fluid mixing properties, helically coiled tubes are widely used in a variety of industries and applications. In fact, helical tubes are the most popular from the family of coiled tube heat exchangers. This review summarises and critically reviews the studies reported in the pertinent literature on the pressure drop characteristics of two-phase flow in helically coiled tubes. The main findings and correlations for the frictional two-phase pressure drops due to: steam-water flow boiling, R-134a evaporation and condensation, air-water two-phase flow and nanofluid flows are reviewed. Therefore, the purpose of this study is to provide researchers in academia and industry with a practical summary of the relevant correlations and supporting theory for the calculation of the two-phase pressure drop in helically coiled tubes. A significant scope for further research was also identified in the fields of: air-water bubbly flow and nanofluid two phase and three-phase flows in helically coiled tubes