mTOR inhibition leads to SRC-mediated EGFR internalisation and degradation in glioma cells

Epidermal Growth Factor receptor (EGFR) is a tyrosine kinase receptor widely expressed on the surface of numerous cell types, which activates several downstream signalling pathways involved in cell proliferation, migration and survival. EGFR alterations, such as overexpression or mutations, have been frequently observed in several cancers, including glioblastoma (GBM), and are associated to uncontrolled cell proliferation. Here we show that the inhibition of mammalian target of Rapamycin (mTOR) mediates EGFR delivery to lysosomes for degradation in GBM cells, independently of autophagy activation. Coherently with EGFR internalisation and degradation, mTOR blockade negatively affects the mitogen activated protein/extracellular signal-regulated kinase (MAPK)/ERK pathway. Furthermore, we provide evidence that Src kinase activation is required for EGFR internaliation upon mTOR inhibition. Our results further support the hypothesis that mTOR targeting may represent an effective therapeutic strategy in GBM management, as its inhibition results in EGFR degradation and in proliferative signal alteration

mTOR inhibition leads to SRC-mediated EGFR internalisation and degradation in glioma cells

Epidermal Growth Factor receptor (EGFR) is a tyrosine kinase receptor widely expressed on the surface of numerous cell types, which activates several downstream signalling pathways involved in cell proliferation, migration and survival. EGFR alterations, such as overexpression or mutations, have been frequently observed in several cancers, including glioblastoma (GBM), and are associated to uncontrolled cell proliferation. Here we show that the inhibition of mammalian target of Rapamycin (mTOR) mediates EGFR delivery to lysosomes for degradation in GBM cells, independently of autophagy activation. Coherently with EGFR internalisation and degradation, mTOR blockade negatively affects the mitogen activated protein/extracellular signal-regulated kinase (MAPK)/ERK pathway. Furthermore, we provide evidence that Src kinase activation is required for EGFR internaliation upon mTOR inhibition. Our results further support the hypothesis that mTOR targeting may represent an effective therapeutic strategy in GBM management, as its inhibition results in EGFR degradation and in proliferative signal alteration

Effect of Noise on Frequency-Resolved Optical Gating Measurements of Ultrashort Pulses

We study the effects of noise in Frequency-Resolved Optical Gating measurements of ultrashort pulses. We quantify the measurement accuracy in the presence of additive, muliplicative, and quantization noise, and discuss filtering and pre-processing of the data

Epidemiological investigation of an acute case of Chagas disease in an area of active transmission in Peruvian Amazon region

The study objective was to investigate an acute case of Chagas disease in the San Pedro de Shishita community, Pebas District, in the Peruvian Amazon basin, a non-endemic area. Both parents of the index case (acute case) were thoroughly interviewed, a seroepidemiological survey was carried out in the community, parasitological exams were carried out only in relatives of the index case, and triatomine bugs were searched for inside houses, peridomiciliary, and in wild environments. Seroprevalence for IgG anti-T. cruzi antibodies was 1/104 (0.96%), using an ELISA test and an indirect immunofluorescence assay. Panstrongylus geniculatus and Rhodnius pictipes adults were found. The index case is autochthonous from San Pedro de Shishita, but the source of transmission is unknown.O objetivo deste trabalho foi estudar caso da doença de Chagas aguda na comunidade indígena de San Pedro de Shishita, sem conhecimento da origem da transmissão. San Pedro de Shishita, distrito Pebas, região da Amazônia peruana é uma área não endêmica. Foram entrevistados os pais do paciente e feito inquérito soroepidemiológico dos participantes e estudos parasitológicos da família e procurou-se também triatomíneos no ambiente doméstico, peridomiciliar e silvestre. A soroprevalência de anticorpos IgG anti-T. cruzi foi 1/ 104 (0,96%) por ELISA e imunofluorescência indireta. Foram encontrados adultos de Panstrongylus geniculatus e Rhodnius pictipe

Sociodemographic Factors Associated with the Satisfaction Level of Peruvian Dental Students with Virtual Classes During the Covid-19 Pandemic: A Prospective Bicentric Study

Ericka Albornoz-Palacios,1 Marysela Ladera-Castañeda,2 Gissela Briceño-Vergel,1 Nancy Córdova-Limaylla,1 Rosa Aroste-Andía,3 Emily Hernández-Huamaní,3 Percy Gavilán-Chávez,3 Miriam Castro-Rojas,2 Luis Cervantes-Ganoza,4 César Cayo-Rojas1 1School of Stomatology, Universidad Privada San Juan Bautista, Lima, Peru; 2Faculty of Dentistry and Postgraduate School, Universidad Nacional Federico Villarreal, Lima, Peru; 3School of Stomatology, Universidad Privada San Juan Bautista, Ica, Peru; 4Faculty of Stomatology, Universidad Inca Garcilaso de la Vega, Lima, PeruCorrespondence: César Cayo-Rojas, Av. Jose Antonio Lavalle Avenue 302-304, (Ex Hacienda Villa), Chorrillos, Lima, Peru, Email [email protected]: The pandemic caused by Covid-19 impacted all areas of social, economic and educational activity. When there is a high risk of spreading highly infectious diseases, education is usually the first service to be suspended. The objective was to evaluate the sociodemographic factors associated with the satisfaction level of Peruvian dental students with virtual classes during the Covid-19 pandemic.Methods: This observational, cross-sectional, analytical study evaluated 237 dental students from the capital city and one Peruvian province using a validated 13-item questionnaire to measure the level of satisfaction with virtual classes. Pearson’s chi-square test and a logit model were used to evaluate the associated factors such as age group, sex, marital status, monthly family income, area of residence, place of origin, occupation and computer use, considering a significance level of p< 0.05.Results: Of all students, 50.6%, 40.1% and 9.3% presented a good, average and poor level of satisfaction, respectively, with the virtual classes received. In addition, those with a monthly family income of less than 500 US dollars were 3.15 times more likely to have poor satisfaction compared to those with a monthly family income of more than 1000 US dollars (AOR = 3.15; 95% CI: 1.23– 8.05). The rest of the variables evaluated were not considered influential factors in the levels of satisfaction with the virtual classes received.Conclusión: Of all students, 50.6% and 9.3% reported good and poor satisfaction with virtual classes during the COVID-19 pandemic, respectively. Monthly family income of less than 500 US dollars was an influential factor. In addition, the variables age group, sex, marital status, area of residence, place of origin, occupation and computer use were not found to be influential factors.Keywords: e-learning, online learning, sociodemographic factors, satisfaction level, virtual classrooms, dentistry, Covid − 1

A Functional Role of RB-Dependent Pathway in the Control of Quiescence in Adult Epidermal Stem Cells Revealed by Genomic Profiling

Continuous cell renewal in mouse epidermis is at the expense of a pool of pluripotent cells that lie in a well defined niche in the hair follicle known as the bulge. To identify mechanisms controlling hair follicle stem cell homeostasis, we developed a strategy to isolate adult bulge stem cells in mice and to define their transcriptional profile. We observed that a large number of transcripts are underexpressed in hair follicle stem cells when compared to non-stem cells. Importantly, the majority of these downregulated genes are involved in cell cycle. Using bioinformatics tools, we identified the E2F transcription factor family as a potential element involved in the regulation of these transcripts. To determine their functional role, we used engineered mice lacking Rb gene in epidermis, which showed increased expression of most E2F family members and increased E2F transcriptional activity. Experiments designed to analyze epidermal stem cell functionality (i.e.: hair regrowth and wound healing) imply a role of the Rb-E2F axis in the control of stem cell quiescence in epidermis

Recent progress in cassava agronomy research in the Philippines

During the last three years cassava production in the Philippines did not progress markedly, neither in area nor in volume. In terms of area, there was only an increase of 14,424 ha or 6.4%, while in terms of volume the increase was 112,177 metric tons or 5.7%. One of the reasons for this was the unstable price for chips, especially in 1994/95. Up to the present, cassava cultivation is still concentrated in Mindanao where there are greater opportunities for marketing, particularly trading of dry chips by the San Miguel Corporation and animal feed millers, as well as fresh roots for production of starch. In terms of research, not much data has been generated, since only very few experiments were conducted. Some experiments were terminated, like the one on cropping systems trials in Negros Occidental. In Leyte the fifth cropping cycle of the long-term fertility trial under coconut showed no significant responses to fertilizers, but there were some responses in the sixth year of consecutive cropping. In the erosion control trial, highest soil losses were observed in plots with application of inorganic fertilizers (14-14-14), while the lowest soil losses were observed in plots with vetiver grass barriers or with grass mulch. Root yields were highest with the application of grass mulch or when Crotalaria juncea was intercropped and mulched at 2 months; yields were lowest in plots with lemon grass barriers. The variety x fertilizer trial in Bontoc, southern Leyte, showed a clear varietal response to fertilizers. The variety with a heavier canopy responded more markedly to fertilizer applications. In an intercropping trial in Bohol, even after three cropping cycles, cassava yields were not significantly affected by interplanting of either soybean, mungbean, cowpea, peanut or pole sitao (yard-long bean). However, row spacing significantly affected the yields of cassava and intercrops. In another trial, marked increases in cassava yields were obtained when the plant densify was increased to 15,000-25,000 plants/ha. On the other hand, no significant differences were observed when the age of pruning cassava was varied

Direct ultrashort-pulse retrieval using frequency-resolved optical gating and a computational neural network

Previously, ultrashort-laser-pulse retrieval in Frequency-Resolved Optical Gating required an iterative algorithm. Here, however, we use a computational neural network for directly recovering pulses