LKB1 induces apical trafficking of Silnoon, a monocarboxylate transporter, in Drosophila melanogaster

Silnoon (Sln) is a monocarboxylate transporter (MCT) that mediates active transport of metabolic monocarboxylates such as butyrate and lactate. Here, we identify Sln as a novel LKB1-interacting protein using Drosophila melanogaster genetic modifier screening. Sln expression does not affect cell cycle progression or cell size but specifically enhances LKB1-dependent apoptosis and tissue size reduction. Conversely, down-regulation of Sln suppresses LKB1-dependent apoptosis, implicating Sln as a downstream mediator of LKB1. The kinase activity of LKB1 induces apical trafficking of Sln in polarized cells, and LKB1-dependent Sln trafficking is crucial for triggering apoptosis induced by extracellular butyrate. Given that LKB1 functions to control both epithelial polarity and cell death, we propose Sln is an important downstream target of LKB1

Cuidados de enfermería a pacientes adultos mayores sometidos a endoscopías altas en los consultorios externos del Hospital Angamos 2010 -2015

El presente informe "Endoscopías digestivas altas en pacientes adultos mayores de los consultorios externos del hospital Angamos 2013 — 2015", tiene como objetivo describir la experiencia profesional del cuidado de enfermería a pacientes adultos mayores con endoscopías digestivas altas en los consultorios externos del Hospital Angamos del 2013 al 2015. Es indiscutible que el desarrollo de nuevas tecnologías como la endoscópica, han tenido un impacto importante sobre la necesidad de los pacientes en realizarse un examen auxiliar, debido las múltiples afecciones que atraviesan en su salud; esta demanda se realiza ambulatoriamente en el consultorio externo de Gastroenterología del Hospital Angamos, y es aquí, donde los profesionales de enfermería se enfrentan a nuevos retos en la atención. Los usuarios, han dejado de ser sujetos pasivos que dejaban enteramente las decisiones de su salud en manos de los profesionales; a ser pacientes demandantes de información, y exigentes de una atención de alta calidad en los cuidados y servicios vinculados a su proceso de enfermedad, reclamando el derecho a formar parte en la toma de decisiones en favor de su salud. Son precisamente los adultos mayores, quienes en su mayoría hacen uso de estos servicios, ya que su salud casi siempre se ve resquebrajada y son muchos los problemas y limitaciones que se presentan en la vejez; por lo cual, se debe tener especial cuidado en su intervención.Trabajo academic

The in vivo Therapeutic Effect of Free Wanderer Powder (逍 遙 散 xiāo yáo sǎn, Xiaoyaosan) on Mice with 4T1 Cell Induced Breast Cancer Model

ABSTRACTIn the present study, we investigated the therapeutic effect of a classical TCM formula, Free Wanderer Powder (逍遙散 xiāo yáo sǎn), in a breast cancer mouse model induced with estrogen-insensitive breast cancer 4T1 cells. Ovariectomized Balb/c mice (6-8 weeks) or sham mice were injected into the fourth mammary fat pad with 4T1 cells in which tumors were palpable 7days after injection. On the eighth day, the mice were divided into 4 groups and tubefed daily with vehicle, Free Wanderer Powder (逍遙散 xiāo yáo sǎn) formula or tamoxifen for 28days. Tumor growth inhibition and the decrease of the average tumor mass were most evident in mice treated with Free Wanderer Powder (逍遙散 xiāo yáo sǎn). Free Wanderer Powder (逍遙散 xiāo yáo sǎn) treatment significantly reduced Bcl-2 and elevated Bax and p53 protein expressions in breast cancer tumor. These results were further confirmed by immunohistochemisty. Tamoxifen could decrease spleen mass and Bcl-2 protein expression, increase the Bax protein expression as well as exert uterotrophic effects by increasing uterus index and inducing the gene expressions in the uterus. Taken together, these results show that Free Wanderer Powder (逍遙散 xiāo yáo sǎn) treatment induced apoptosis at protein level and inhibited the tumor growth in 4T1-induced ovariectomized Balb/c female mice, indicating the possibility of its future use for treatment of estrogen-insensitive breast caner

Sexual Relationship Power and Depression among HIV-Infected Women in Rural Uganda

Background: Depression is associated with increased HIV transmission risk, increased morbidity, and higher risk of HIV-related death among HIV-infected women. Low sexual relationship power also contributes to HIV risk, but there is limited understanding of how it relates to mental health among HIV-infected women. Methods: Participants were 270 HIV-infected women from the Uganda AIDS Rural Treatment Outcomes study, a prospective cohort of individuals initiating antiretroviral therapy (ART) in Mbarara, Uganda. Our primary predictor was baseline sexual relationship power as measured by the Sexual Relationship Power Scale (SRPS). The primary outcome was depression severity, measured with the Hopkins Symptom Checklist (HSCL), and a secondary outcome was a functional scale for mental health status (MHS). Adjusted models controlled for socio-demographic factors, CD4 count, alcohol and tobacco use, baseline WHO stage 4 disease, social support, and duration of ART. Results: The mean HSCL score was 1.34 and 23.7% of participants had HSCL scores consistent with probable depression (HSCL>1.75). Compared to participants with low SRPS scores, individuals with both moderate (coefficient b = −0.21; 95%CI, −0.36 to −0.07) and high power (b = −0.21; 95%CI, −0.36 to −0.06) reported decreased depressive symptomology. High SRPS scores halved the likelihood of women meeting criteria for probable depression (adjusted odds ratio = 0.44; 95%CI, 0.20 to 0.93). In lagged models, low SRPS predicted subsequent depression severity, but depression did not predict subsequent changes in SPRS. Results: were similar for MHS, with lagged models showing SRPS predicts subsequent mental health, but not visa versa. Both Decision-Making Dominance and Relationship Control subscales of SRPS were associated with depression symptom severity. Conclusions: HIV-infected women with high sexual relationship power had lower depression and higher mental health status than women with low power. Interventions to improve equity in decision-making and control within dyadic partnerships are critical to prevent HIV transmission and to optimize mental health of HIV-infected women

Cultured circulating tumor cells and their derived xenografts for personalized oncology

AbstractRecent cancer research has demonstrated the existence of circulating tumor cells (CTCs) in cancer patient's blood. Once identified, CTC biomarkers will be invaluable tools for clinical diagnosis, prognosis and treatment. In this review, we propose ex vivo culture as a rational strategy for large scale amplification of the limited numbers of CTCs from a patient sample, to derive enough CTCs for accurate and reproducible characterization of the biophysical, biochemical, gene expressional and behavioral properties of the harvested cells. Because of tumor cell heterogeneity, it is important to amplify all the CTCs in a blood sample for a comprehensive understanding of their role in cancer metastasis. By analyzing critical steps and technical issues in ex vivo CTC culture, we developed a cost-effective and reproducible protocol directly culturing whole peripheral blood mononuclear cells, relying on an assumed survival advantage in CTCs and CTC-like cells over the normal cells to amplify this specified cluster of cancer cells

Effect and mechanism of lipopolysaccharide on allergen-induced interleukin-5 and eotaxins production by whole blood cultures of atopic asthmatics

Interleukin (IL)-5 and eotaxin families regulate the development of eosinophilic inflammation of asthma in a co-operative manner. The exposure to airborne lipopolysaccharide (LPS) induces varying degrees of airflow obstruction and neutrophilic airway inflammation. Production of IL-5 and eotaxin subfamily chemokines was analysed in response to Dermatophagoides pteronyssinus allergen (D.p.) according to the presence of specific IgE to D.p., and investigated the mechanism underlying their LPS-mediated regulation of these cytokines in response to the specific allergen. Peripheral blood cells (PBCs) from asthmatics with (group 1) or without (group 2) specific IgE to D.p. and from non-asthmatics with (group 3) or without (group 4) were stimulated with D.p. or LPS. For LPS-mediated inhibition of IL-5 and eotaxin-2 production, LPS-induced cytokines were added to the D.p.-stimulated PBCs. IL-5 and eotaxin-2, but not eotaxin-1 and 3, were significantly increased by D.p.-stimulated-PBCs from group 1, while only eotaxin-2 was elevated in group 3. Eotaxin-2 production was found in monocytes and correlated with the level of specific IgE to D.p. LPS treatment resulted in the decrease in eotaxin-2 and IL-5 production by the D.p.-stimulated PBCs. LPS-induced IL-10 completely inhibited D.p.-stimulated production of eotaxin-2 and IL-5. The differential responses of the eotaxin family to specific antigens suggest that the predominant role of eotaxin-2 and LPS may attenuate eosinophilic inflammation by inhibiting IL-5 and eotaxin-2 synthesis through IL-10 production

MRI-based porosity index (PI) and suppression ratio (SR) in the tibial cortex show significant differences between normal, osteopenic, and osteoporotic female subjects

IntroductionUltrashort echo time (UTE) MRI enables quantitative assessment of cortical bone. The signal ratio in dual-echo UTE imaging, known as porosity index (PI), as well as the signal ratio between UTE and inversion recovery UTE (IR-UTE) imaging, known as the suppression ratio (SR), are two rapid UTE-based bone evaluation techniques developed to reduce the time demand and cost in future clinical studies. The goal of this study was to investigate the performance of PI and SR in detecting bone quality differences between subjects with osteoporosis (OPo), osteopenia (OPe), and normal bone (Normal).MethodsTibial midshaft of fourteen OPe (72 ± 6 years old), thirty-one OPo (72 ± 6 years old), and thirty-seven Normal (36 ± 19 years old) subjects were scanned using dual-echo UTE and IR-UTE sequences on a clinical 3T scanner. Measured PI, SR, and bone thickness were compared between OPo, OPe, and normal bone (Normal) subjects using the Kruskal–Wallis test by ranks. Spearman’s rank correlation coefficients were calculated between dual-energy x-ray absorptiometry (DEXA) T-score and UTE-MRI results.ResultsPI was significantly higher in the OPo group compared with the Normal (24.1%) and OPe (16.3%) groups. SR was significantly higher in the OPo group compared with the Normal (41.5%) and OPe (21.8%) groups. SR differences between the OPe and Normal groups were also statistically significant (16.2%). Cortical bone was significantly thinner in the OPo group compared with the Normal (22.0%) and OPe (13.0%) groups. DEXA T-scores in subjects were significantly correlated with PI (R=-0.32), SR (R=-0.50), and bone thickness (R=0.51).DiscussionPI and SR, as rapid UTE-MRI-based techniques, may be useful tools to detect and monitor bone quality changes, in addition to bone morphology, in individuals affected by osteoporosis

Multiplexed Quantum Dot Labeling of Activated c-Met Signaling in Castration-Resistant Human Prostate Cancer

The potential application of multiplexed quantum dot labeling (MQDL) for cancer detection and prognosis and monitoring therapeutic responses has attracted the interests of bioengineers, pathologists and cancer biologists. Many published studies claim that MQDL is effective for cancer biomarker detection and useful in cancer diagnosis and prognosis, these studies have not been standardized against quantitative biochemical and molecular determinations. In the present study, we used a molecularly characterized human prostate cancer cell model exhibiting activated c-Met signaling with epithelial to mesenchymal transition (EMT) and lethal metastatic progression to bone and soft tissues as the gold standard, and compared the c-Met cell signaling network in this model, in clinical human prostate cancer tissue specimens and in a castration-resistant human prostate cancer xenograft model. We observed c-Met signaling network activation, manifested by increased phosphorylated c-Met in all three. The downstream survival signaling network was mediated by NF-κB and Mcl-1 and EMT was driven by receptor activator of NF-κB ligand (RANKL), at the single cell level in clinical prostate cancer specimens and the xenograft model. Results were confirmed by real-time RT-PCR and western blots in a human prostate cancer cell model. MQDL is a powerful tool for assessing biomarker expression and it offers molecular insights into cancer progression at both the cell and tissue level with high degree of sensitivity

Targeted NGS gene panel identifies mutations in RSPH1 causing primary ciliary dyskinesia and a common mechanism for ciliary central pair agenesis due to radial spoke defects.

Primary ciliary dyskinesia (PCD) is an inherited chronic respiratory obstructive disease with randomized body laterality and infertility, resulting from cilia and sperm dysmotility. PCD is characterized by clinical variability and extensive genetic heterogeneity, associated with different cilia ultrastructural defects and mutations identified in >20 genes. Next generation sequencing (NGS) technologies therefore present a promising approach for genetic diagnosis which is not yet in routine use. We developed a targeted panel-based NGS pipeline to identify mutations by sequencing of selected candidate genes in 70 genetically undefined PCD patients. This detected loss-of-function RSPH1 mutations in four individuals with isolated central pair (CP) agenesis and normal body laterality, from two unrelated families. Ultrastructural analysis in RSPH1-mutated cilia revealed transposition of peripheral outer microtubules into the 'empty' CP space, accompanied by a distinctive intermittent loss of the central pair microtubules. We find that mutations in RSPH1, RSPH4A and RSPH9, which all encode homologs of components of the 'head' structure of ciliary radial spoke complexes identified in Chlamydomonas, cause clinical phenotypes that appear to be indistinguishable except at the gene level. By high-resolution immunofluorescence we identified a loss of RSPH4A and RSPH9 along with RSPH1 from RSPH1-mutated cilia, suggesting RSPH1 mutations may result in loss of the entire spoke head structure. CP loss is seen in up to 28% of PCD cases, in whom laterality determination specified by CP-less embryonic node cilia remains undisturbed. We propose this defect could arise from instability or agenesis of the ciliary central microtubules due to loss of their normal radial spoke head tethering

Novel features of ARS selection in budding yeast Lachancea kluyveri

<p>Abstract</p> <p>Background</p> <p>The characterization of DNA replication origins in yeast has shed much light on the mechanisms of initiation of DNA replication. However, very little is known about the evolution of origins or the evolution of mechanisms through which origins are recognized by the initiation machinery. This lack of understanding is largely due to the vast evolutionary distances between model organisms in which origins have been examined.</p> <p>Results</p> <p>In this study we have isolated and characterized autonomously replicating sequences (ARSs) in <it>Lachancea kluyveri </it>- a pre-whole genome duplication (WGD) budding yeast. Through a combination of experimental work and rigorous computational analysis, we show that <it>L. kluyveri </it>ARSs require a sequence that is similar but much longer than the ARS Consensus Sequence well defined in <it>Saccharomyces cerevisiae</it>. Moreover, compared with <it>S. cerevisiae </it>and <it>K. lactis</it>, the replication licensing machinery in <it>L. kluyveri </it>seems more tolerant to variations in the ARS sequence composition. It is able to initiate replication from almost all <it>S. cerevisiae </it>ARSs tested and most <it>Kluyveromyces lactis </it>ARSs. In contrast, only about half of the <it>L. kluyveri </it>ARSs function in <it>S. cerevisiae </it>and less than 10% function in <it>K. lactis</it>.</p> <p>Conclusions</p> <p>Our findings demonstrate a replication initiation system with novel features and underscore the functional diversity within the budding yeasts. Furthermore, we have developed new approaches for analyzing biologically functional DNA sequences with ill-defined motifs.</p