Search

Simple Summary: Cancer is increasingly viewed as a cell cycle disease in that the dysregulation of the cell cycle machinery is a common feature in cancer. The Hippo signaling pathway consists of a core kinase cascade as well as extended regulators, which together control organ size and tissue homeostasis. The aberrant expression of cell cycle regulators and/or Hippo pathway components contributes to cancer development, and for this reason, we specifically focus on delineating the roles of the Hippo pathway in the cell cycle. Improving our understanding of the Hippo pathway from a cell cycle perspective could be used as a powerful weapon in the cancer battlefield. Cell cycle progression is an elaborate process that requires stringent control for normal cellular function. Defects in cell cycle control, however, contribute to genomic instability and have become a characteristic phenomenon in cancers. Over the years, advancement in the understanding of disrupted cell cycle regulation in tumors has led to the development of powerful anti-cancer drugs. Therefore, an in-depth exploration of cell cycle dysregulation in cancers could provide therapeutic avenues for cancer treatment. The Hippo pathway is an evolutionarily conserved regulator network that controls organ size, and its dysregulation is implicated in various types of cancers. Although the role of the Hippo pathway in oncogenesis has been widely investigated, its role in cell cycle regulation has not been comprehensively scrutinized. Here, we specifically focus on delineating the involvement of the Hippo pathway in cell cycle regulation. To that end, we first compare the structural as well as functional conservation of the core Hippo pathway in yeasts, flies, and mammals. Then, we detail the multi-faceted aspects in which the core components of the mammalian Hippo pathway and their regulators affect the cell cycle, particularly with regard to the regulation of E2F activity, the G1 tetraploidy checkpoint, DNA synthesis, DNA damage checkpoint, centrosome dynamics, and mitosis. Finally, we briefly discuss how a collective understanding of cell cycle regulation and the Hippo pathway could be weaponized in combating cancer. [ABSTRACT FROM AUTHOR]

Presents perspectives on issues and problems that impact the verification and validation of knowledge-based systems. Reasons why verification and validation of knowledge-based systems is difficult; Techniques and tools developed for performing verification and validation activities.

The nature of the binding sites for lipopolysaccharide (LPS) on human monocytes was investigated using fluorescein isothiocyanate (FITC)-labelled LPS from Salmonella minnesota R595 (ReLPS). in the absence of serum, ReLPS bound to monocytes and this interaction was trypsin sensitive. A concentration of 0.1 mg/ml resulted in a 90% loss of LPS binding, while low concentrations increased this binding. Trypsin-treated monocytes recovered FITC-ReLPS binding after 20 hr culture, which was abrogated in the presence of cycloheximide and actinomycin D. This showed that de novo protein and mRNA synthesis were essential. A number of different proteins have been implicated in cellular binding of LPS to monocytes. In this paper we show that CD14 is not involved in direct binding of FITC-ReLPS to monocytes, since anti-CD14 monoclonal antibody (mAb) (3C10) and removal of most of cell-surface CD14 by phosphatidylinositol-specific phospholipase C did not prevent FITCReLPS binding. Furthermore, LPS also bound to CD14-deficient cells from a patient with paroxysmal nocturnal haemoglobinuria (PNH). FITC-ReLPS binding was not mediated by the CD11/CD18 complex since mAb to the α and β chains of the CD11/CD18 complex did not alter the binding of FITC-ReLPS to cells. These observations indicate that ReLPS may interact with monocyte membrane protein(s) in the absence of serum. This binding site(s) for LPS might be different from those previously described by others. [ABSTRACT FROM AUTHOR]

The mechanical discontinuities in the upper crust (i.e., faults and related fractures) lead to the uprising of geothermal fluids to the Earth's surface. If fluids are enriched in Ca2+ and HCO3-, masses of CaCO3 (i.e., travertine deposits) can form mainly due to the CO2 leakage from the thermal waters. Among other things, fissure-ridge-type deposits are peculiar travertine bodies made of bedded carbonate that gently to steeply dip away from the apical part where a central fissure is located, corresponding to the fracture trace intersecting the substratum; these morpho-tectonic features are the most useful deposits for tectonic and paleoseismological investigation, as their development is contemporaneous with the activity of faults leading to the enhancement of permeability that serves to guarantee the circulation of fluids and their emergence. Therefore, the fissure ridge architecture sheds light on the interplay among fault activity, travertine deposition, and ridge evolution, providing key geo-chronologic constraints due to the fact that travertine can be dated by different radiometric methods. In recent years, studies dealing with travertine fissure ridges have been considerably improved to provide a large amount of information. In this paper, we report the state of the art of knowledge on this topic refining the literature data as well as adding original data, mainly focusing on the fissure ridge morphology, internal architecture, depositional facies, growth mechanisms, tectonic setting in which the fissure ridges develop, and advantages of using the fissure ridges for neotectonic and seismotectonic studies. [ABSTRACT FROM AUTHOR]

Four streams in the Guadiana watershed were followed up to assess hydrogeomorphological and physicochemical characteristics, and to analyze its correlation with land use/land cover (LULC), analyzing their possible influence in reservoir water quality and possible influence in the reservoir water quality. The highest amounts of organic descriptors and nutrients were quantified in streams with the major percentage of olive groves and vineyards and urban land cover classes. Streams more influenced by agro-silvo-pastoral class presented better water quality, as this type of LULC acts as a buffer of the contamination runoff. The results highlighted that the hydrogeomorphology of the streams may influence the transfer of pollutants loads to reservoirs. Hence, in intermittent streams characterized by coarse particles in the sediment, high amounts of pollutants are accumulated when the flow ceases, and are further transported to the reservoirs when the flow retakes. On the contrary, streams with sediments characterized by a great percentage of fine particles and organic matter do not induce so much stress in reservoirs, since these allow the adsorption of nutrients and trace elements, without their transfer to reservoirs. [ABSTRACT FROM AUTHOR]

Already installed cables are aging and the cable network is growing rapidly. Improved condition monitoring methods are required for greater visibility of insulation defects in the cable networks. One of the critical challenges for continuous monitoring is the large amount of partial discharge (PD) data that poses constraints on the diagnostic capabilities. This paper presents the performance comparison of two data acquisition techniques based on phase resolved partial discharge (PRPD) and pulse acquisition (PA). The major contribution of this work is to provide an in-depth understanding of these techniques considering the perspective of randomness of the PD mechanism and improvements in the reliability of diagnostics. Experimental study is performed on the medium voltage (MV) cables in the laboratory environment. It has been observed that PRPD based acquisition not only requires a significantly larger amount of data but is also susceptible to losing the important information especially when multiple PD sources are being investigated. On the other hand, the PA technique presents improved performance for PD diagnosis. Furthermore, the use of the PA technique enables the efficient practical implementation of the continuous PD monitoring by reducing the amount of data that is acquired by extracting useful signals and discarding the silent data intervals. [ABSTRACT FROM AUTHOR]

Damage to the annulus fibrosus (AF), the outer region of the intervertebral disc (IVD), results in an undesirable condition that may accelerate IVD degeneration causing low back pain. Despite intense research interest, attempts to regenerate the IVD have failed so far and no effective strategy has translated into a successful clinical outcome. Of particular significance, the failure of strategies to repair the AF has been a major drawback in the regeneration of IVD and nucleus replacement. It is unlikely to secure regenerative mediators (cells, genes, and biomolecules) and artificial nucleus materials after injection with an unsealed AF, as IVD is exposed to significant load and large deformation during daily activities. The AF defects strongly change the mechanical properties of the IVD and activate catabolic routes that are responsible for accelerating IVD degeneration. Therefore, there is a strong need to develop effective therapeutic strategies to prevent or reconstruct AF damage to support operational IVD regenerative strategies and nucleus replacement. By the way of this review, repair and regenerative strategies for AF reconstruction, their current status, challenges ahead, and future outlooks were discussed. [ABSTRACT FROM AUTHOR]

Tunneling nanotubes (TNTs) are thin membrane elongations among the cells that mediate the trafficking of subcellular organelles, biomolecules, and cues. Mesenchymal stem cells (MSCs) receive substantial attention in tissue engineering and regenerative medicine. Many MSCs-based clinical trials are ongoing for dreadful diseases including cancer and neurodegenerative diseases. Mitochondrial trafficking through TNTs is one of the mechanisms used by MSCs to repair tissue damage and to promote tissue regeneration. Preclinical studies linked with ischemia, oxidative stress, mitochondrial damage, inflammation, and respiratory illness have demonstrated the therapeutic efficacy of MSCs via TNTs-mediated transfer of mitochondria and other molecules into the injured cells. On the other hand, MSCs-based cancer studies showed that TNTs may modulate chemoresistance in tumor cells as a result of mitochondrial trafficking. In the present review, we discuss the role of TNTs from preclinical studies associated with MSCs treatment. We discuss the impact of TNTs formation between MSCs and cancer cells and emphasize to study the importance of TNTs-mediated MSCs protection in disease models. [ABSTRACT FROM AUTHOR]

Mobile devices have penetrated all spheres of human activities, including education. Previous research has shown that smartphones are becoming widely used in learning as they can improve knowledge retention and increase student engagement. The purpose of this study was to discuss students' perception of the use of a mobile application aimed at learning new English vocabulary and phrases and describe its strengths and weaknesses as perceived by the students. In total, 28 university students answered a pen and paper questionnaire survey after experiencing the app during one semester. Overall, the students' agreement to the positive aspects displayed in the questionnaire prevailed over their disagreement or neutral opinions. The mobile app helped students prepare for the final achievement test, learning was accessible from anywhere and at any time, students appreciated the corrective feedback and would opt for the implementation of the mobile app in other courses taught at the faculty. On the other hand, as the findings indicate, the students reported that the app was not very supportive regarding communication performance; they did not find the teachers' notifications encouraging and they did not use the pronunciation support much, which was caused by various factors, such as offering students words and phrases without context or not testing all the items in the final credit test. The findings of this study contribute to the existing knowledge of students' perceptions of the use of mobile apps for learning purposes. [ABSTRACT FROM AUTHOR]

In this study, we reviewed articles on technology-enhanced language learning and teaching. We aimed to summarize the content of reviewed articles in the following categories: (1) the number of articles published by journals and by year; (2) languages and skills; (3) technology used; (4) promising technologies. We reviewed 398 research articles. The highest number of articles was published in 2017 (n = 80), whereas the lowest number was published in 2014 (n = 53). The Computer Assisted Language Learning journal published the highest number of articles (n = 100), whereas the lowest number of published articles appeared in IEEE Transactions on Learning Technologies (n = 3). The most common target language was English (n = 267). Writing, speaking, and vocabulary gained the most attention in published articles. Twenty-three different technologies were identified and they were used 406 times. Based on our results, we made several implications and suggestions for future studies. This review study can serve as a guide for teaching and research communities who plan on designing language learning and teaching activities supported by technologies. [ABSTRACT FROM AUTHOR]

Background: The Golgi apparatus undergoes disorganization in response to stress, but it is able to restore compact and perinuclear structure under recovery. This self-organization mechanism is significant for cellular homeostasis, but remains mostly elusive, as does the role of giantin, the largest Golgi matrix dimeric protein. Methods: In HeLa and different prostate cancer cells, we used the model of cellular stress induced by Brefeldin A (BFA). The conformational structure of giantin was assessed by proximity ligation assay and atomic force microscopy. The post-BFA distribution of Golgi resident enzymes was examined by 3D SIM high-resolution microscopy. Results: We detected that giantin is rather flexible than an extended coiled-coil dimer and BFA-induced Golgi disassembly was associated with giantin monomerization. A fusion of the nascent Golgi membranes after BFA washout is forced by giantin re-dimerization via disulfide bond in its luminal domain and assisted by Rab6a GTPase. GM130-GRASP65-dependent enzymes are able to reach the nascent Golgi membranes, while giantin-sensitive enzymes appeared at the Golgi after its complete recovery via direct interaction of their cytoplasmic tail with N-terminus of giantin. Conclusion: Post-stress recovery of Golgi is conducted by giantin dimer and Golgi proteins refill membranes according to their docking affiliation rather than their intra-Golgi location. [ABSTRACT FROM AUTHOR]

The ubiquitously expressed family of inward rectifier potassium (KIR) channels, encoded by KCNJ genes, is primarily involved in cell excitability and potassium homeostasis. Channel mutations associate with a variety of severe human diseases and syndromes, affecting many organ systems including the central and peripheral neural system, heart, kidney, pancreas, and skeletal muscle. A number of mutations associate with altered ion channel expression at the plasma membrane, which might result from defective channel trafficking. Trafficking involves cellular processes that transport ion channels to and from their place of function. By alignment of all KIR channels, and depicting the trafficking associated mutations, three mutational hotspots were identified. One localized in the transmembrane-domain 1 and immediately adjacent sequences, one was found in the G-loop and Golgi-export domain, and the third one was detected at the immunoglobulin-like domain. Surprisingly, only few mutations were observed in experimentally determined Endoplasmic Reticulum (ER)exit-, export-, or ER-retention motifs. Structural mapping of the trafficking defect causing mutations provided a 3D framework, which indicates that trafficking deficient mutations form clusters. These "mutation clusters" affect trafficking by different mechanisms, including protein stability. [ABSTRACT FROM AUTHOR]

Power transformers are the most important assets of electric power substations. The reliability in the operation of electric power transmission and distribution is due to the correct operation and maintenance of power transformers. The parameters that are most used to assess the health status of power transformers are dissolved gas analysis (DGA), oil quality analysis (OQA) and content of furfuraldehydes (FFA) in oil. The parameter that currently allows for simple online monitoring in an energized transformer is the DGA. Although most of the DGA continues to be done in the laboratory, the trend is online DGA monitoring, since it allows for detection or diagnosis of the faults throughout the life of the power transformers. This study presents a review of the main DGA monitors, single- or multi-gas, their most important specifications, accuracy, repeatability and measurement range, the types of installation, valve or closed loop, and number of analogue inputs and outputs. This review shows the differences between the main existing DGA monitors and aims to help in the selection of the most suitable DGA monitoring approach according to the needs of each case. [ABSTRACT FROM AUTHOR]

Rainfall patterns in the San Francisco Bay Area (SFBA) are highly influenced by local topography. It has been a forecasting challenge for the main US forecast models. This study investigates the ability of the Weather Research and Forecasting (WRF) model to improve upon forecasts, with particular emphasis on the rain shadow common to the southern end of the SFBA. Three rain events were evaluated: a mid-season atmospheric river (AR) event with copious rains; a typical non-AR frontal passage rain event; and an area-wide rain event in which zero rain was recorded in the southern SFBA. The results show that, with suitable choices of parameterizations, the WRF model with a resolution around 1 km can forecast the observed rainfall patterns with good accuracy, and would be suitable for operational use, especially to water and emergency managers. Additionally, the three synoptic situations were investigated for further insight into the common ingredients for either flooding rains or strong rain shadow events. [ABSTRACT FROM AUTHOR]

The epithelial cells in an adult woman's breast tissue are continuously replaced throughout their reproductive life during pregnancy and estrus cycles. Such extensive epithelial cell turnover is governed by the primitive mammary stem cells (MaSCs) that proliferate and differentiate into bipotential and lineage-restricted progenitors that ultimately generate the mature breast epithelial cells. These cellular processes are orchestrated by tightly-regulated paracrine signals and crosstalk between breast epithelial cells and their tissue microenvironment. However, current evidence suggests that alterations to the communication between MaSCs, epithelial progenitors and their microenvironment plays an important role in breast carcinogenesis. In this article, we review the current knowledge regarding the role of the breast tissue microenvironment in regulating the special functions of normal and cancer stem cells. Understanding the crosstalk between MaSCs and their microenvironment will provide new insights into how an altered breast tissue microenvironment could contribute to breast cancer development, progression and therapy response and the implications of this for the development of novel therapeutic strategies to target cancer stem cells. [ABSTRACT FROM AUTHOR]

Low back pain (LBP), commonly induced by intervertebral disc degeneration, is a lumbar disease with worldwide prevalence. However, the mechanism of degeneration remains unclear. The intervertebral disc is a nonvascular organ consisting of three components: Nucleus pulposus, annulus fibrosus, and endplate cartilages. The disc is structured to support our body motion and endure persistent external mechanical pressure. Thus, there is a close connection between force and intervertebral discs in LBP. It is well established that with aging, disordered mechanical stress profoundly influences the fate of nucleus pulposus and the alignment of collagen fibers in the annulus fibrosus. These support a new understanding that disordered mechanical stress plays an important role in the degeneration of the intervertebral discs. Tissue-engineered regenerative and reparative therapies are being developed for relieving disc degeneration and symptoms of lower back pain. In this paper, we will review the current literature available on the role of disordered mechanical stress in intervertebral disc degeneration, and evaluate the existing tissue engineering treatment strategies of the current therapies. [ABSTRACT FROM AUTHOR]

The development and growth of vertebrate axial muscle have been studied for decades at both the descriptive and molecular level. The zebrafish has provided an attractive model system for investigating both muscle patterning and growth due to its simple axial musculature with spatially separated fibre types, which contrasts to complex muscle groups often deployed in amniotes. In recent years, new findings have reshaped previous concepts that define how final teleost muscle form is established and maintained. Here, we summarise recent findings in zebrafish embryonic myogenesis with a focus on fibre type specification, followed by an examination of the molecular mechanisms that control muscle growth with emphasis on the role of the dermomyotome-like external cell layer. We also consider these data sets in a comparative context to gain insight into the evolution of axial myogenic patterning systems within the vertebrate lineage. [ABSTRACT FROM AUTHOR]

In power converters, the fast switching of the power conversion components results in rapid changes in voltage and current, which results in oscillations and high-level electromagnetic interference (EMI), so the power components become a source of internal electromagnetic interference. Taking SiC Metal-Oxide-Semiconductor Field-Effect Transistor (MOSFET) as an example, an intelligent control method to suppressing interference sources is proposed in this paper. The combination of open-loop and closed-loop methods can simultaneously reduce the electromagnetic interference generated by voltage and current. Firstly, this paper analyzes how to select a reference signal. The relationship between the time domain and the frequency domain of the noise signal is analyzed. The convolution of the trapezoidal signal and the Gaussian signal is selected as the reference signal, which is named S-shaped signal in this paper. The S-shaped signal has continuous infinitely conductive characteristics, so its spectrum has a large attenuation in the high frequency region. Secondly, a new topology is proposed. Based on the closed-loop gate control, a current control signal is added, which can simultaneously shape the output voltage and control the output current slope. Both the simulation results and the experimental results show that the output voltage can follow the reference signal, S-shaped signal, and the slope and overshoot of output current can be changed. Compared with classical gate driver method, the spectrum of output voltage and output current obtained by the method proposed in this paper has a large attenuation, in other words, the electromagnetic interference is significantly reduced. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests that gamma-tocotrienol (γ-T3), a vitamin E isomer, has potent anti-cancer properties against a wide-range of cancers. γ-T3 not only inhibited the growth and survival of cancer cells in vitro, but also suppressed angiogenesis and tumour metastasis under in vivo conditions. Recently, γ-T3 was found to target cancer stem cells (CSCs), leading to suppression of tumour formation and chemosensitisation. Despite its promising anti-cancer potential, the exact mechanisms responsible for the effects of γ-T3 are still largely unknown. Here, we report the identification of Ang-1 (Angiopoietin-1)/Tie-2 as a novel γ-T3 downstream target. In prostate cancer cells, γ-T3 treatment leads to the suppression of Ang-1 at both the mRNA transcript and protein levels. Supplementing the cells with Ang-1 was found to protect them against the anti-CSC effect of γ-T3. Intriguingly, inactivation of Tie-2, a member receptor that mediates the effect of Ang-1, was found to significantly enhance the cytotoxic effect of γ-T3 through activation of AMP-activated protein kinase (AMPK) and subsequent interruption of autophagy. Our results highlighted the therapeutic potential of using γ-T3 in combination with a Tie-2 inhibitor to treat advanced prostate cancer. [ABSTRACT FROM AUTHOR]

Ion channels are transmembrane proteins that conduct specific ions across biological membranes. Ion channels are present at the onset of many cellular processes, and their malfunction triggers severe pathologies. Potassium channels (KChs) share a highly conserved signature that is necessary to conduct K+ through the pore region. To be functional, KChs require an exquisite regulation of their subcellular location and abundance. A wide repertoire of signatures facilitates the proper targeting of the channel, fine-tuning the balance that determines traffic and location. These signature motifs can be part of the secondary or tertiary structure of the protein and are spread throughout the entire sequence. Furthermore, the association of the pore-forming subunits with different ancillary proteins forms functional complexes. These partners can modulate traffic and activity by adding their own signatures as well as by exposing or masking the existing ones. Post-translational modifications (PTMs) add a further dimension to traffic regulation. Therefore, the fate of a KCh is not fully dependent on a gene sequence but on the balance of many other factors regulating traffic. In this review, we assemble recent evidence contributing to our understanding of the spatial expression of KChs in mammalian cells. We compile specific signatures, PTMs, and associations that govern the destination of a functional channel. [ABSTRACT FROM AUTHOR]

A 16 year old Chinese female with puerperal ovarian vein thrombophlebitis following uneventful vaginal delivery is reported. This infrequent, but potentially fatal, complication in the febrile postpartum patient may present as a surgical emergency. Non-invasive diagnostic procedures and conservative treatment with heparinization and antibiotics have been suggested. However, early exploratory laparotomy for ovarian vein or caval ligation may be life-saving if the diagnosis is in doubt or the response to conservative treatment is unsuccessful. [ABSTRACT FROM PUBLISHER]

Objective: We studied the urinary sediment mRNA level of Th9- and Th22-related cytokines in patients with systemic lupus erythematosus (SLE)., Methods: We quantified urinary mRNA levels of interleukin (IL) 9, IL-10, IL-22, and their corresponding transcription factors in 73 patients with active lupus nephritis, 13 patients with hypertensive nephrosclerosis (HTN), and 25 healthy subjects., Results: There was no detectable IL-9 mRNA in all samples. Patients with proliferative lupus nephritis had significantly lower urinary IL-22 mRNA levels than those with nonproliferative nephritis (2.2 ± 5.4 vs 8.6 ± 20.0 copies, p = 0.019), and urinary IL-22 mRNA level inversely correlated with the histological activity index (r = -0.427, p < 0.0001). In contrast, patients with lupus nephritis had significantly higher urinary IL-10 mRNA levels than patients with HTN (7.8 ± 18.5 vs 1.9 ± 4.0 copies, p = 0.012), and urinary IL-10 mRNA levels correlated with its intrarenal mRNA levels (r = 0.337, p = 0.004) and SLE disease activity index (r = 0.277, p = 0.018). Urinary IL-10 mRNA level was significantly lower among patients who achieved complete remission than those with partial remission or no response (4.1 ± 6.5 vs 14.1 ± 28.0 copies, p = 0.036)., Conclusion: Urinary IL-22 mRNA level is decreased in patients with SLE with proliferative nephritis, while urinary IL-10 mRNA levels correlates with its intrarenal mRNA level and disease activity. Urinary IL-10 mRNA levels may also predict treatment response. These results suggest that urinary mRNA levels of IL-10 and IL-22 might be used as biomarkers for assessing disease activity and risk stratification in lupus nephritis.