Dynamin- and Rab5-Dependent Endocytosis of a Ca²⁺-Activated K⁺ Channel, KCa2.3

Regulation of the number of ion channels at the plasma membrane is a critical component of the physiological response. We recently demonstrated that the Ca2+-activated K+ channel, KCa2.3 is rapidly endocytosed and enters a Rab35- and EPI64C-dependent recycling compartment. Herein, we addressed the early endocytic steps of KCa2.3 using a combination of fluorescence and biotinylation techniques. We demonstrate that KCa2.3 is localized to caveolin-rich domains of the plasma membrane using fluorescence co-localization, transmission electron microscopy and co-immunoprecipitation (co-IP). Further, in cells lacking caveolin-1, we observed an accumulation of KCa2.3 at the plasma membrane as well as a decreased rate of endocytosis, as assessed by biotinylation. We also demonstrate that KCa2.3 and dynamin II are co-localized following endocytosis as well as demonstrating they are associated by co-IP. Further, expression of K44A dynamin II resulted in a 2-fold increase in plasma membrane KCa2.3 as well as a 3-fold inhibition of endocytosis. Finally, we evaluated the role of Rab5 in the endocytosis of KCa2.3. We demonstrate that expression of a dominant active Rab5 (Q79L) results in the accumulation of newly endocytosed KCa2.3 on to the membrane of the Rab5-induced vacuoles. We confirmed this co-localization by co-IP; demonstrating that KCa2.3 and Rab5 are associated. As expected, if Rab5 is required for the endocytosis of KCa2.3, expression of a dominant negative Rab5 (S34N) resulted in an approximate 2-fold accumulation of KCa2.3 at the plasma membrane. This was confirmed by siRNA-mediated knockdown of Rab5. Expression of the dominant negative Rab5 also resulted in a decreased rate of KCa2.3 endocytosis. These results demonstrate that KCa2.3 is localized to a caveolin-rich domain within the plasma membrane and is endocytosed in a dynamin- and Rab5-dependent manner prior to entering the Rab35/EPI64C recycling compartment and returning to the plasma membrane. © 2012 Gao et al

La gestión eficaz del docente en el aula. Un estudio de caso.

The quality of education is one of the purposes of our educational system, struggled to achieve effective schools where the figure of the teacher acquires rightful role in classroom management and educational improvement. These is a research focused on teaching management of new teachers and experts and learns about and compare different ways of managing the classroom teachers employed by these groups and classrooms with similar characteristics. After the statistical treatments of the data have been checked three of the hypotheses, two were rejected and partially confirmed.La dirección direction calidad educativa es uno de los Propósitos de Nuestro Sistema Educativo, lidiado Por CONSEGUIR Escuelas Eficaces Donde la Figura del Docente Adquiera el papel Que le corresponde en la Gestión del aula y en la Mejora Educativa. En Esta Investigación se Analiza la Gestión Docente de noveles y Expertos, en Grupos y aulas de SIMILARES Características, a través de dos Instrumentos:. Uno de Observación Directa Y OTRO indirecta Tras el Tratamiento Estadístico de los Datos se han comprobado tres de las hipótesis planteadas, dos fueron rechazadas y uña parcialmente confirmada

Multimodal treatment of myophasal chronic pelvic pain in women: institutional experience

Background: Chronic pelvic pain of myofascial origin is an underdiagnosed condition and with partial responses to the different treatment modalities. The objective of this study was to report the results of the multimodal management of Myofascial Chronic Pelvic Pain.Methods: Retrospective cohort of 33 patients with myofascial chronic pelvic pain, during the period 01 January 2016 to August 31, 2018, who were treated based on trigger point infiltration and analgesic vaginal electrostimulation. The analogous visual pain scale (VAS) was used at the beginning, sixth, twelfth and six months after the last electrostimulation session, in order to measure the effect of the treatment.Results: During the study period, 32 patients with chronic myofascial pelvic pain were found who received the multimodal scheme that is offered in our clinic. The average score of the EVA before starting the treatment was 8.5 points, at the sixth session of the treatment the average EVA was 3.6 points, at the twelfth session of 1.3 points and the average score of the EVA at six months after the last session of the multimodal treatment was 2.9 points. A significant difference was demonstrated in the average EVA score in the first with respect to the sixth, twelfth and six months (p = <0.000). There were no complications or adverse effects secondary to the multimodal treatment.Conclusions: Multimodal treatment was associated with progressive improvement in 80% of patients with miofascial chronic pelvic pain

Pelvic floor dysfunction in Mexican women

Background: Pelvic floor dysfunction (PFD) is a term used to describe a variety of disorders that involve moderate to severe impairment of the pelvic floor muscles. Throughout their lives, up to 46% of women will present at least one form of PFD and may even have a combination of this pathology. These afflictions have a profound influence on women’s general well-being and quality of life, as well as being an immense economic burden for global health systems. Methods: This was a populational study which used surveys made in Google Forms of different questionnaires validated in Spanish [Urinary Incontinence Questionnaire (ICIQ), Female Sexual Function Index (IFSF), CPPQ Questionnaire for chronic pelvic pain, Wexner anal incontinence scale and quality of life] which were taken by women with access to social networks and who agreed to carry out an anonymous survey. Results: Seven hundred and twenty-one participants were evaluated, a total of 61.4% (443) responded positively to involuntary loss of urine, 35% had presented discomfort during sexual activity or lack of sexual interest, 14% had genital pain and 16% reported involuntary loss of feces or gas. Of all the patients that answered any of these questioners positively, only 33% had sought medical attention in the past. Conclusions: We concluded that in our population PFD is underdiagnosed. Our populations prevalence of urinary incontinence and pelvic pain is within the internationally described margins; anal incontinence is above international reports, and our population presented a lower prevalence of sexual dysfunction. With this new information we must impulse awareness to guide various preventive behaviors

Lower urinary tract symptoms secondary to a vaginal leiomioma the female prostate: case report

This is a case report of lower urinary tract symptoms secondary to a vaginal leiomioma “the female prostate”. A 45-year-old female patient with no significant personal history, sensation of a vaginal foreign body accompanied by lower urinary tract symptoms, on vaginal physical examination with a 7×7 cm deep tumor, increased consistency, not painful, without hemorrhage. Magnetic resonance imaging with hypointense T1 and T2 images, few linear hyperintense areas in T2, homogeneous postgadolinium enhancement 69×66×53 mm, solid tumor dependent on the vaginal vault. Tumor markers CA 19-9: 5.98 U/ml, CEA: 1.09 ng/ml and CA 125: 11.73 U/ml. Open surgery was performed in which a 8×6 cm tumor was found in the vaginal vault dependent on the posterior wall of the vagina. Histopathological report: conventional leiomyoma measuring 9×7.5 cm in long axes, without nuclear atypia. With resolution of symptoms in the lower urinary tract, with normal urinary frequency, without presence of urgency, without urinary incontinence or voiding symptoms. It is important to identify and diagnose lower urinary tract symptoms always, since they could be an initial manifestation of pelvic tumors in which the treatment approach should not be delayed.

LHC sensitivity to the resonance spectrum of a minimal strongly interacting electroweak symmetry breaking sector

We present a unified analysis of the two main production processes of vector boson pairs at the LHC, VV-fusion and qqbar annihilation, in a minimal strongly interacting electroweak symmetry breaking sector. Using a unitarized electroweak chiral Lagrangian formalism and modeling the final V_L V_L strong rescattering effects by a form factor, we describe qqbar annihilation processes in terms of the two chiral parameters that govern elastic V_L V_L scattering. Depending on the values of these two chiral parameters, the unitarized amplitudes may present resonant enhancements in different angular momentum-isospin channels. Scanning this two parameter space, we generate the general resonance spectrum of a minimal strongly interacting electroweak symmetry breaking sector and determine the regions that can be probed at the LHC.Comment: Final version to appear in Phys. Rev. D, including a more detailed exposition and a few more references. Conclusions and results unchanged. 14 pages, 5 figure

IKK phosphorylates Huntingtin and targets it for degradation by the proteasome and lysosome

Expansion of the polyglutamine repeat within the protein Huntingtin (Htt) causes Huntington's disease, a neurodegenerative disease associated with aging and the accumulation of mutant Htt in diseased neurons. Understanding the mechanisms that influence Htt cellular degradation may target treatments designed to activate mutant Htt clearance pathways. We find that Htt is phosphorylated by the inflammatory kinase IKK, enhancing its normal clearance by the proteasome and lysosome. Phosphorylation of Htt regulates additional post-translational modifications, including Htt ubiquitination, SUMOylation, and acetylation, and increases Htt nuclear localization, cleavage, and clearance mediated by lysosomal-associated membrane protein 2A and Hsc70. We propose that IKK activates mutant Htt clearance until an age-related loss of proteasome/lysosome function promotes accumulation of toxic post-translationally modified mutant Htt. Thus, IKK activation may modulate mutant Htt neurotoxicity depending on the cell's ability to degrade the modified species

Hyperspectral imaging benchmark based on machine learning for intraoperative brain tumour detection

publishedVersio

GSE4‐loaded nanoparticles a potential therapy for lung fibrosis that enhances pneumocyte growth, reduces apoptosis and DNA damage

Idiopathic pulmonary fibrosis is a lethal lung fibrotic disease, associated with aging with a mean survival of 2-5 years and no curative treatment. The GSE4 peptide is able to rescue cells from senescence, DNA and oxidative damage, inflammation, and induces telomerase activity. Here, we investigated the protective effect of GSE4 expression in vitro in rat alveolar epithelial cells (AECs), and in vivo in a bleomycin model of lung fibrosis. Bleomycin-injured rat AECs, expressing GSE4 or treated with GSE4-PLGA/PEI nanoparticles showed an increase of telomerase activity, decreased DNA damage, and decreased expression of IL6 and cleaved-caspase 3. In addition, these cells showed an inhibition in expression of fibrotic markers induced by TGF-β such as collagen-I and III among others. Furthermore, treatment with GSE4-PLGA/PEI nanoparticles in a rat model of bleomycin-induced fibrosis, increased telomerase activity and decreased DNA damage in proSP-C cells. Both in preventive and therapeutic protocols GSE4-PLGA/PEI nanoparticles prevented and attenuated lung damage monitored by SPECT-CT and inhibited collagen deposition. Lungs of rats treated with bleomycin and GSE4-PLGA/PEI nanoparticles showed reduced expression of α-SMA and pro-inflammatory cytokines, increased number of pro-SPC-multicellular structures and increased DNA synthesis in proSP-C cells, indicating therapeutic efficacy of GSE4-nanoparticles in experimental lung fibrosis and a possible curative treatment for lung fibrotic patients

Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector

A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13  TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139  fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV