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ESR1 mutations: Moving towards guiding treatment decision-making in metastatic breast cancer patients
No full textAbstractMutations in the gene coding for the estrogen receptor (ER), ESR1, have been associated with acquired endocrine resistance in patients with ER-positive metastatic breast cancer (MBC). Functional studies revealed that these ESR1 mutations lead to constitutive activity of the ER, meaning that the receptor is active in absence of its ligand estrogen, conferring resistance against several endocrine agents. While recent clinical studies reported that the occurrence of ESR1 mutations is rare in primary breast cancer tumors, these mutations are more frequently observed in metastatic tissue and circulating cell-free DNA of MBC patients pretreated with endocrine therapy. Given the assumed impact that the presence of ESR1 mutations has on outcome to endocrine therapy, assessing ESR1 mutations in MBC patients is likely to be of significant interest to further individualize treatment for MBC patients. Here, ESR1 mutation detection methods and the most relevant pre-clinical and clinical studies on ESR1 mutations regarding endocrine resistance are reviewed, with particular interest in the ultimate goal of guiding treatment decision-making based on ESR1 mutations
Breast cancer-secreted miR-939 downregulates VE-cadherin and destroys the barrier function of endothelial monolayers
No full textAbstractExosomes-secreted microRNAs play an important role in metastatic spread. During this process breast cancer cells acquire the ability to transmigrate through blood vessels by inducing changes in the endothelial barrier. We focused on miR-939 that is predicted to target VE-cadherin, a component of adherens junction involved in vessel permeability. By in silico analysis miR-939 was found highly expressed in the basal-like tumor subtypes and in our cohort of 63 triple-negative breast cancers (TNBCs) its expression significantly interacted with lymph node status in predicting disease-free survival probability. We demonstrated, in vitro, that miR-939 directly targets VE-cadherin leading to an increase in HUVECs monolayer permeability. MDA-MB-231 cells transfected with a miR-939 mimic, released miR-939 in exosomes that, once internalized in endothelial cells, favored trans-endothelial migration of MDA-MB-231-GFP cells by the disruption of the endothelial barrier. Notably, when up taken in endothelial cells exosomes caused VE-cadherin down-regulation specifically through miR-939 as we demonstrated by inhibiting miR-939 expression in exosomes-releasing TNBC cells.Together, our data indentify an extracellular pro-tumorigenic role for tumor-derived, exosome-associated miR-939 that can explain its association with worse prognosis in TNBCs
The influence of two-point statistics on the Hashin–Shtrikman bounds for three phase composites
No full textAbstractIn this work we analyse the influence of the spatial distribution function, introduced by Ponte Castañeda and Willis (1995), on the Hashin–Shtrikman bounds on the effective transport properties of a transversely isotropic (TI) three-phase particulate composite, i.e. when two distinct materials are embedded in a matrix medium. We provide a straightforward mechanism to construct associated bounds, independently accounting for the shape, size and spatial distribution of the respective phases, and assuming ellipsoidal symmetry.The main novelty in the present scheme resides in the consideration of more than a single inclusion phase type. Indeed, unlike the two-phase case, a two-point correlation function is necessary to characterize the spatial distribution of the inclusion phases in order to avoid overlap between different phase types. Moreover, once the interaction between two different phases is described, the scheme developed can straightforwardly be extended to multiphase composites.The uniform expression for the associated Hill tensors and the use of a proper tensor basis set, leads to an explicit set of equations for the bounds. This permits its application to a wide variety of phenomena governed by Laplace’s operator. Some numerical implementations are provided to validate the effectiveness of the scheme by comparing the predictions with available experimental data and other theoretical results
Role of ethylene and the APETALA 2/ethylene response factor superfamily in rice under various abiotic and biotic stress conditions
No full textAbstractEthylene, the simplest gaseous plant growth regulator (PGR), controls diverse physiological pathways in plants. Under various stress conditions and during different developmental stages, such as root elongation, leaf and flower senescence, seed germination, tissue differentiation and organ abscission, ethylene biosynthesis is significantly increased. In rice, the internal ethylene concentration is rapidly regulated to a genetically, physiologically and morphologically relevant level under various stresses. Regulation of the ethylene signalling pathway under adverse conditions results in up- and/or down-regulation of the expression of stress-related genes in different families. Transcription factors are proteins that influence and control a number of biological processes under both normal and stress conditions. APETALA 2/ethylene response factor (AP2/ERF) is a transcription factor that is considered to function in stress response pathways in rice. To date, many AP2/ERF genes have been functionally characterised in rice. An understanding of the interactions between the AP2/ERF genes and ethylene-dependent mechanisms may provide new insights to facilitate the enhanced adaptation of rice to stress. In the current review, the structure and function of ethylene in rice under normal and stress conditions are described, and then the general functions of the plant AP2/ERF transcription factors are discussed. In addition, the interactions between the AP2/ERF genes and ethylene pathways under abiotic stresses, including submergence, cold, salinity, drought and heavy metal stresses, as well as those under biotic stresses, are summarised. Although the AP2/ERF genes have been identified, information on the physiological mechanisms of this gene family under stress conditions in rice remains limited. Therefore, further physiological studies must be performed in the future to identify additional features of this crucial gene family
Adsorption characteristics of sulfur powder by bamboo charcoal to restrain sulfur allergies
No full textAbstractExposures to particulate matter with a diameter of 2.5μm or less (PM2.5) may influence the risk of birth defects and make you allergic, which causes serious harm to human health. Bamboo charcoal can adsorb harmful substances,that was of benefitto people’s health. In order to figure out the optimal adsorbtion condition and the intrinsic change of bamboo charcoal, five chemicals were adsorbed by bamboo charcoal and were analyzed by FT-IR. The optimal blast time was 80min of Na2SO3, 100min of Na2S2O8, 20min of Na2SO4, 120min of Fe2(SO4)3 and 60min or 100min of S. FT-IR spectra showed that bamboo charcoal had five characteristic peaks of SS stretch, H2O stretch, OH stretch, CO stretch or CC stretch, and NO2 stretch at 3850cm−1, 3740cm−1, 3430cm−1, 1630cm−1 and 1530cm−1, respectively. For Na2SO3, the peaks at 3850cm−1, 3740cm−1, 3430cm−1, 1630cm−1 and 1530cm−1 achieved the maximum at 20min. For Na2S2O8, the peaks at 3850cm−1, 3740cm−1, 3430cm−1and1530cm−1 achieved the maximum at 40min. For Na2SO4, the peaks at 3850cm−1, 3740cm−1and1530cm−1 achieved the maximum at 40min. For Fe2(SO4)3, the peaks at 3850cm−1, 3740cm−1, 1630cm−1 and 1530cm−1 achieved the maximum at 120min. For S, the peaks at 3850cm−1 and 3740cm−1 achieved the maximum at 40min, the peaks at 1630cm−1 and 1530cm−1 achieved the maximum at 40min.It proved that bamboo charcoal could remove sulfur powder from air to restrain sulfur allergies
Effects of noise exposure on young adults with normal audiograms I: Electrophysiology
No full textAbstractNoise-induced cochlear synaptopathy has been demonstrated in numerous rodent studies. In these animal models, the disorder is characterized by a reduction in amplitude of wave I of the auditory brainstem response (ABR) to high-level stimuli, whereas the response at threshold is unaffected. The aim of the present study was to determine if this disorder is prevalent in young adult humans with normal audiometric hearing. One hundred and twenty six participants (75 females) aged 18–36 were tested. Participants had a wide range of lifetime noise exposures as estimated by a structured interview. Audiometric thresholds did not differ across noise exposures up to 8 kHz, although 16-kHz audiometric thresholds were elevated with increasing noise exposure for females but not for males. ABRs were measured in response to high-pass (1.5 kHz) filtered clicks of 80 and 100 dB peSPL. Frequency-following responses (FFRs) were measured to 80 dB SPL pure tones from 240 to 285 Hz, and to 80 dB SPL 4 kHz pure tones amplitude modulated at frequencies from 240 to 285 Hz (transposed tones). The bandwidth of the ABR stimuli and the carrier frequency of the transposed tones were chosen to target the 3–6 kHz characteristic frequency region which is usually associated with noise damage in humans. The results indicate no relation between noise exposure and the amplitude of the ABR. In particular, wave I of the ABR did not decrease with increasing noise exposure as predicted. ABR wave V latency increased with increasing noise exposure for the 80 dB peSPL click. High carrier-frequency (envelope) FFR signal-to-noise ratios decreased as a function of noise exposure in males but not females. However, these correlations were not significant after the effects of age were controlled. The results suggest either that noise-induced cochlear synaptopathy is not a significant problem in young, audiometrically normal adults, or that the ABR and FFR are relatively insensitive to this disorder in young humans, although it is possible that the effects become more pronounced with age
Climate policy integration in the land use sector: Mitigation, adaptation and sustainable development linkages
No full textAbstractThis article re-conceptualizes Climate Policy Integration (CPI) in the land use sector to highlight the need to assess the level of integration of mitigation and adaptation objectives and policies to minimize trade-offs and to exploit synergies. It suggests that effective CPI in the land use sector requires i) internal climate policy coherence between mitigation and adaptation objectives and policies; ii) external climate policy coherence between climate change and development objectives; iii) vertical policy integration to mainstream climate change into sectoral policies and; iv) horizontal policy integration by overarching governance structures for cross-sectoral coordination. This framework is used to examine CPI in the land use sector of Indonesia. The findings indicate that adaptation actors and policies are the main advocates of internal policy coherence. External policy coherence between mitigation and development planning is called for, but remains to be operationalized. Bureaucratic politics has in turn undermined vertical and horizontal policy integration. Under these circumstances it is unlikely that the Indonesian bureaucracy can deliver strong coordinated action addressing climate change in the land use sector, unless sectoral ministries internalize a strong mandate on internal and external climate policy coherence and find ways to coordinate policy action effectively
Comparative study of wavelet-ARIMA and wavelet-ANN models for temperature time series data in northeastern Bangladesh
No full textAbstractTime-series analyses of temperature data are important for investigating temperature variation and predicting temperature change. Here, Mann–Kendall (M–K) analyses of temperature time-series data in northeastern Bangladesh indicated increasing trends (Sen’s slope of maximum and minimum yearly temperature at Sylhet of 0.03°C and 0.026°C, respectively, and a minimum temperature at Sreemangal of 0.024°C) except for the maximum temperature at Sreemangal. The linear trends showed that the maximum temperature is increasing by 2.97°C and 0.59°C per hundred years, and the minimum, by 2.17°C and 2.73°C per hundred years at the Sylhet and Sreemangal stations, indicating that climate change is affecting temperature in this area. This paper presents an alternative method for temperature prediction by combining the wavelet technique with an autoregressive integrated moving average (ARIMA) model and an artificial neural network (ANN) applied to monthly maximum and minimum temperature data. The data are divided into a training dataset (1957–2000) to construct the models and a testing dataset (2001–2012) to estimate their performance. The calibration and validation performance of the models is evaluated statistically, and the relative performance based on the predictive capability of out-of-sample forecasts is assessed. The results indicate that the wavelet-ARIMA model is more effective than the wavelet-ANN model
The impact of arbuscular mycorrhizal fungi in mitigating salt-induced adverse effects in sweet basil (Ocimum basilicum L.)
No full textAbstractSalinity is one of the serious abiotic stresses adversely affecting the majority of arable lands worldwide, limiting the crop productivity of most of the economically important crops. Sweet basil (Osmium basilicum) plants were grown in a non-saline soil (EC=0.64dSm−1), in low saline soil (EC=5dSm−1), and in a high saline soil (EC=10dSm−1). There were differences between arbuscular mycorrhizal (Glomus deserticola) colonized plants (+AMF) and non-colonized plants (−AMF). Mycorrhiza mitigated the reduction of K, P and Ca uptake due to salinity. The balance between K/Na and between Ca/Na was improved in +AMF plants. Growth enhancement by mycorrhiza was independent from plant phosphorus content under high salinity levels. Different growth parameters, salt stress tolerance and accumulation of proline content were investigated, these results showed that the use of mycorrhizal inoculum (AMF) was able to enhance the productivity of sweet basil plants under salinity conditions. Mycorrhizal inoculation significantly increased chlorophyll content and water use efficiency under salinity stress. The sweet basil plants appeared to have high dependency on AMF which improved plant growth, photosynthetic efficiency, gas exchange and water use efficiency under salinity stress. In this study, there was evidence that colonization with AMF can alleviate the detrimental salinity stress influence on the growth and productivity of sweet basil plants
Synthesizing time-evolving partially-coherent Schell-model sources
No full textAbstractTime-evolving simulation of sources with partial spatial and temporal coherence is sometimes instructive or necessary to explain optical coherence effects. Yet, existing time-evolving synthesis techniques often require prohibitive amounts of computer memory. This paper discusses three methods for the synthesis of continuous or pulsed time-evolving sources with nearly arbitrary spatial and temporal coherence. One method greatly reduces computer memory requirements, making this type of synthesis more practical. The utility of all three methods is demonstrated via a modified form of Young's experiment. Numerical simulation and laboratory results for time-averaged irradiance are presented and compared with theory to validate the synthesis techniques