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https://www.readbyqxmd.com/read/28647367/mitochondrial-quality-control-pathways-pink1-acts-as-a-gatekeeper
#1
Elvira P Leites, Vanessa A Morais
Mitochondria have a pivotal role in the maintenance of cell homeostasis and survival. Mitochondria are involved in processes such as ATP production, reactive oxygen species production, apoptosis induction, calcium homeostasis and protein degradation. Thus, mechanisms that regulate the intrinsic quality of mitochondria have a crucial role in dictating overall cell fate. The importance of these well-regulated mechanisms is highlighted in disease scenarios such as neurodegeneration, cancer and neuromuscular atrophy...
June 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28646105/the-glycolytic-enzyme-phosphofructokinase-1-assembles-into-filaments
#2
Bradley A Webb, Anne M Dosey, Torsten Wittmann, Justin M Kollman, Diane L Barber
Despite abundant knowledge of the regulation and biochemistry of glycolytic enzymes, we have limited understanding on how they are spatially organized in the cell. Emerging evidence indicates that nonglycolytic metabolic enzymes regulating diverse pathways can assemble into polymers. We now show tetramer- and substrate-dependent filament assembly by phosphofructokinase-1 (PFK1), which is considered the "gatekeeper" of glycolysis because it catalyzes the step committing glucose to breakdown. Recombinant liver PFK1 (PFKL) isoform, but not platelet PFK1 (PFKP) or muscle PFK1 (PFKM) isoforms, assembles into filaments...
June 23, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28634726/connexin-channels-at-the-glio-vascular-interface-gatekeepers-of-the-brain
#3
Marijke De Bock, Luc Leybaert, Christian Giaume
Neuronal survival, electrical signaling and synaptic activity require a well-balanced micro-environment in the central nervous system. This is achieved by the blood-brain barrier (BBB), an endothelial barrier situated in the brain capillaries, that controls near-to-all passage in and out of the brain. The endothelial barrier function is highly dependent on signaling interactions with surrounding glial, neuronal and vascular cells, together forming the neuro-glio-vascular unit. Within this functional unit, connexin (Cx) channels are of utmost importance for intercellular communication between the different cellular compartments...
June 20, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28630320/%C3%AE-20-ifitm2-differentially-restricts-x4-and-r5-hiv-1
#4
Wan-Lin Wu, Christopher Robert Grotefend, Ming-Ting Tsai, Yi-Ling Wang, Vladimir Radic, Hyungjin Eoh, I-Chueh Huang
CCR5 (R5)-tropic, but not CXCR4 (X4)-tropic, HIV-1 is associated with primary HIV-1 infection and transmission. Recent studies have shown that IFN-induced transmembrane (IFITM) proteins, including IFITM1, IFITM2, and IFITM3, restrict a broad range of viruses. Here, we demonstrate that an IFITM2 isoform (Δ20 IFITM2) lacking 20 amino acids at the N terminus differentially restricts X4 and R5 HIV-1. Δ20 IFITM2 suppresses replication of X4 HIV-1 strains by inhibiting their entry. High levels of Δ20 IFITM2 expression could be detected in CD4(+) T cells and in monocytes...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28622609/the-strategic-defense-of-physician-autonomy-state-public-health-agencies-as-countervailing-powers
#5
Laura Senier, Rachael Lee, Lauren Nicoll
Advances in genetic testing and the aggressive marketing of genetic tests by commercial diagnostic laboratories have driven both consumer demand and the need for unbiased information about how tests should guide healthcare delivery. This paper uses the countervailing powers framework to explore the role of state public health agencies as arbiters of quality and safety, specifically through their efforts to encourage physicians to follow evidence-based recommendations for screening for hereditary cancers. Social scientists have often viewed actions by the state to regulate cost, quality, or safety as a threat to physician autonomy...
June 3, 2017: Social Science & Medicine
https://www.readbyqxmd.com/read/28622403/using-network-sampling-and-recruitment-data-to-understand-social-structures-related-to-community-health-in-a-population-of-people-who-inject-drugs-in-rural-puerto-rico
#6
Mayra Coronado-García, Courtney R Thrash, Melissa Welch-Lazoritz, Robin Gauthier, Juan Carlos Reyes, Bilal Khan, Kirk Dombrowski
OBJECTIVE: This research examined the social network and recruitment patterns of a sample of people who inject drugs (PWIDs) in rural Puerto Rico, in an attempt to uncover systematic clustering and between-group social boundaries that potentially influence disease spread. METHODS: Respondent driven sampling was utilized to obtain a sample of PWID in rural Puerto Rico. Through eight initial "seeds", 317 injection drug users were recruited. Using recruitment patterns of this sample, estimates of homophily and affiliation were calculated using RDSAT...
June 2017: Puerto Rico Health Sciences Journal
https://www.readbyqxmd.com/read/28620581/third-generation-tyrosine-kinase-inhibitors-targeting-epidermal-growth-factor-receptor-mutations-in-non-small-cell-lung-cancer
#7
REVIEW
Tristan A Barnes, Grainne M O'Kane, Mark David Vincent, Natasha B Leighl
Sensitizing mutations in the epidermal growth factor receptor (EGFR) predict response to EGFR tyrosine kinase inhibitors (TKIs) and both first- and second-generation TKIs are available as first-line treatment options in patients with advanced EGFR-mutant non-small cell lung cancer. Eventual resistance develops with multiple mechanisms identifiable both upon repeat biopsy and in plasma circulating tumor DNA. The T790M gatekeeper mutation is responsible for almost 60% of cases. A number of third-generation TKIs are in clinical development, and osimertinib has been approved by the US Food and Drug Administration for the treatment of patients with EGFR T790M mutant lung cancer after failure of initial EGFR kinase therapy...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28619646/time-dependent-effects-of-hjp272-an-endothelin-receptor-antagonist-in-bleomycin-induced-pulmonary-fibrosis
#8
Xingjian Liu, Nikhil Khadtare, Hardek Patel, Ralph Stephani, Jerome Cantor
Using a lipopolysaccharide (LPS) model of acute lung injury, we have previously shown that endothelin-1 (ET-1), a potent mediator of vasoconstriction, may act as a "gatekeeper" for the influx of inflammatory cells into the lung. To further investigate the potential of ET-1 to limit the progression of lung injury, hamsters were treated with an endothelin receptor antagonist (ERA), HJP272, either 1 h prior to intratracheal instillation of bleomycin (BLM) or 24 h afterwards. Lung injury and repair were examined by measuring the following parameters: 1) histopathological changes; 2) neutrophil content in bronchoalveolar lavage fluid (BALF); 3) lung collagen content; 4) tumor necrosis factor receptor 1 (TNFR1) expression by BALF macrophages; 5) BALF levels of: a) transforming growth factor beta-1 (TGF-β1), b) stromal cell-derived factor 1 (commonly referred to as CXCL12), and c) platelet-derived growth factor BB (PDGF-BB); 6) alveolar septal cell apoptosis (as measured by the TUNEL assay)...
June 12, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28615132/identification-of-a-secondary-mutation-in-the-kit-kinase-domain-correlated-with-imatinib-resistance-in-a-canine-mast-cell-tumor
#9
Yuko Nakano, Masato Kobayashi, Makoto Bonkobara, Masamine Takanosu
Imatinib-resistance is a major therapeutic problem in human chronic myeloid leukemia, human gastrointestinal stromal tumors, and canine mast cell tumors. In the present study, we identified the secondary mutation c.2006C>T in c-KIT exon 14 in a mast cell tumor obtained from a dog carrying c.1663-1671del in exon 11 and showing resistance to imatinib. The mutation in exon 14 resulted in substitution of threonine with isoleucine at position 669, which was located at the center of the ATP binding site as a gatekeeper and played an important role in binding to imatinib...
June 2017: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/28614421/zero-calcium-score-as-a-filter-for-further-testing-in-patients-admitted-to-the-coronary-care-unit-with-chest-pain
#10
Luis Cláudio Lemos Correia, Fábio P Esteves, Manuela Carvalhal, Thiago Menezes Barbosa de Souza, Nicole de Sá, Vitor Calixto de Almeida Correia, Felipe Kalil Beirão Alexandre, Fernanda Lopes, Felipe Ferreira, Márcia Noya-Rabelo
Background: The accuracy of zero coronary calcium score as a filter in patients with chest pain has been demonstrated at the emergency room and outpatient clinics, populations with low prevalence of coronary artery disease (CAD). Objective: To test the gatekeeping role of zero calcium score in patients with chest pain admitted to the coronary care unit (CCU), where the pretest probability of CAD is higher than that of other populations. Methods: Patients underwent computed tomography for calcium scoring, and obstructive CAD was defined by a minimum 70% stenosis on invasive angiography...
June 12, 2017: Arquivos Brasileiros de Cardiologia
https://www.readbyqxmd.com/read/28610603/an-australian-indigenous-community-led-suicide-intervention-skills-training-program-community-consultation-findings
#11
Bushra Nasir, Steve Kisely, Leanne Hides, Geetha Ranmuthugala, Sharon Brennan-Olsen, Geoffrey C Nicholson, Neeraj S Gill, Noel Hayman, Srinivas Kondalsamy-Chennakesavan, Maree Toombs
BACKGROUND: Little is known of the appropriateness of existing gatekeeper suicide prevention programs for Indigenous communities. Despite the high rates of Indigenous suicide in Australia, especially among Indigenous youth, it is unclear how effective existing suicide prevention programs are in providing appropriate management of Indigenous people at risk of suicide. METHODS: In-depth, semi-structured interviews and focus groups were conducted with Indigenous communities in rural and regional areas of Southern Queensland...
June 13, 2017: BMC Psychiatry
https://www.readbyqxmd.com/read/28608999/specimen-acquisition-roses-gardeners-and-gatekeepers
#12
Adele O Kraft
The use of minimally invasive procedures for diagnosis and treatment decisions means that very often cytological samples are the only material available for testing. Cytology has evolved from a strictly morphological approach to the routine use of immunohistochemistry. The advent of personalized medicine has increased the demand for molecular testing, making rapid on-site evaluation even more relevant. This article presents current rapid on-site evaluation practice patterns in different settings, with a special focus on the variety of professionals involved...
June 2017: Cancer
https://www.readbyqxmd.com/read/28603078/gatekeepers-in-the-healthcare-sector-knowledge-and-bourdieu-s-concept-of-field
#13
Fran M Collyer, Karen F Willis, Sophie Lewis
Choice is an imperative for patients in the Australian healthcare system. The complexity of this healthcare 'maze', however, means that successfully navigating and making choices depends not only on the decisions of patients, but also other key players in the healthcare sector. Utilising Bourdieu's concepts of capital, habitus and field, we analyse the role of gatekeepers (i.e., those who control access to resources, services and knowledge) in shaping patients' experiences of healthcare, and producing opportunities to enable or constrain their choices...
June 3, 2017: Social Science & Medicine
https://www.readbyqxmd.com/read/28597858/policy-and-governance-to-address-depression-and-suicide-in-bhutan-the-national-suicide-prevention-strategy
#14
Gampo Dorji, Sonam Choki, Kinga Jamphel, Yeshi Wangdi, Tandin Chogyel, Chencho Dorji, Damber Kumar Nirola
Suicide and mental disorders are a growing public health issue in Bhutan, due in part to a rapidly transitioning society. The burden of suicide has been recognized by the Royal Government of Bhutan and, as a result, it introduced the country's first ever national suicide-prevention plan in 2015. The 3-year action plan takes a holistic approach to making suicide-prevention services a top social priority, through strengthening suicide-prevention policies, promoting socially protective measures, mitigating risk factors and reaching out to individuals who are at risk of suicide or affected by incidents of suicide...
April 2017: WHO South-East Asia Journal of Public Health
https://www.readbyqxmd.com/read/28597856/challenges-and-opportunities-in-suicide-prevention-in-south-east-asia
#15
Lakshmi Vijayakumar
Suicide is a global public health problem, with over 800 000 people worldwide dying by suicide in 2012, according to the World Health Organization (WHO). The WHO South-East Asia Region is especially affected, with 39% of global suicides occurring in the 11 countries in this region. Women are a particularly vulnerable population, for a variety of social and cultural reasons. In India specifically, deaths by suicide for women peak in the age range 15-29 years. There is sufficient evidence to show that reduction of easy access to means of suicide is an effective prevention strategy...
April 2017: WHO South-East Asia Journal of Public Health
https://www.readbyqxmd.com/read/28591583/distinct-thalamic-reticular-cell-types-differentially-modulate-normal-and-pathological-cortical-rhythms
#16
Alexandra Clemente-Perez, Stefanie Ritter Makinson, Bryan Higashikubo, Scott Brovarney, Frances S Cho, Alexander Urry, Stephanie S Holden, Matthew Wimer, Csaba Dávid, Lief E Fenno, László Acsády, Karl Deisseroth, Jeanne T Paz
Integrative brain functions depend on widely distributed, rhythmically coordinated computations. Through its long-ranging connections with cortex and most senses, the thalamus orchestrates the flow of cognitive and sensory information. Essential in this process, the nucleus reticularis thalami (nRT) gates different information streams through its extensive inhibition onto other thalamic nuclei, however, we lack an understanding of how different inhibitory neuron subpopulations in nRT function as gatekeepers...
June 6, 2017: Cell Reports
https://www.readbyqxmd.com/read/28589692/a-gatekeeping-procedure-to-test-a-primary-and-a-secondary-endpoint-in-a-group-sequential-design-with-multiple-interim-looks
#17
Ajit C Tamhane, Jiangtao Gou, Christopher Jennison, Cyrus R Mehta, Teresa Curto
Glimm et al. (2010) and Tamhane et al. (2010) studied the problem of testing a primary and a secondary endpoint, subject to a gatekeeping constraint, using a group sequential design (GSD) with K=2 looks. In this article, we greatly extend the previous results to multiple (K>2) looks. If the familywise error rate (FWER) is to be controlled at a preassigned α level then it is clear that the primary boundary must be of level α. We show under what conditions one α-level primary boundary is uniformly more powerful than another...
June 6, 2017: Biometrics
https://www.readbyqxmd.com/read/28585456/potential-conflicts-in-midwifery-practice-regarding-conscientious-objection-to-abortions-in-scotland
#18
Valerie Fleming, Yvonne Robb
BACKGROUND: This study was developed as a result of a court case involving conflicts between midwives' professional practice and their faith when caring for women undergoing abortions in Scotland. RESEARCH QUESTIONS: What are practising Roman Catholics' perspectives of potential conflicts between midwives' professional practice in Scotland with regard to involvement in abortions and their faith? How relevant is the 'conscience clause' to midwifery practice today? and What are participants' understandings of Canon 1398 in relation to midwifery practice? RESEARCH DESIGN: The theoretical underpinning of this study was Gadamer's hermeneutic out of which the method developed by Fleming et al...
January 1, 2017: Nursing Ethics
https://www.readbyqxmd.com/read/28583614/effects-of-active-immunization-against-gnrh-versus-surgical-castration-on-hypothalamic-pituitary-function-in-boars
#19
Xingfa Han, Yuqin Zhou, Yu Zeng, Fenfen Sui, Yacheng Liu, Yao Tan, Xiaohan Cao, Xiaogang Du, Fengyan Meng, Xianyin Zeng
The objective was to compare effects of anti-GnRH immunization (immunocastration) versus surgical castration on hypothalamic-pituitary function in boars. Thirty-six boars were randomly divided into three groups (n = 12/group): control, surgically castrated, or immunized against GnRH at 10 wk of age (boostered 8 wk later). Compared to intact boars, immunocastration reduced (P < 0.05) serum concentrations of LH, FSH, testosterone and inhibin B and caused severe testicular atrophy, whereas surgical castration increased (P < 0...
July 15, 2017: Theriogenology
https://www.readbyqxmd.com/read/28579957/the-epigenomics-of-embryonic-pathway-signaling-in-colorectal-cancer
#20
REVIEW
Curt Balch, Jayaram B Ramapuram, Amit K Tiwari
Colorectal cancer (CRC) is the second-leading cause of cancer death in developed countries. While early detection (e.g., colonoscopy) generally yields excellent outcomes, metastatic and drug-resistant disease is uniformly fatal, and non-compliance for screening remains over 25%. Familial CRCs (10% of total cases) primarily include mutations in the gene APC. Somatic disease is linked to several environmental several risk factors, including mutations in WNT, KRAS, and TGFβ. To reflect the genesis/progression of CRC, a series of five discrete stages, from normal colon mucosa to fully invasive carcinoma, each regulated by specific "gatekeeper" genes, remains well-accepted after 20 years...
2017: Frontiers in Pharmacology
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