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https://www.readbyqxmd.com/read/28344334/the-kif1a-homolog-unc-104-is-important-for-spontaneous-release-postsynaptic-density-maturation-and-perisynaptic-scaffold-organization
#1
Yao V Zhang, Shabab B Hannan, Jeannine V Kern, Doychin T Stanchev, Baran Koç, Thomas R Jahn, Tobias M Rasse
The kinesin-3 family member KIF1A has been shown to be important for experience dependent neuroplasticity. In Drosophila, amorphic mutations in the KIF1A homolog unc-104 disrupt the formation of mature boutons. Disease associated KIF1A mutations have been associated with motor and sensory dysfunctions as well as non-syndromic intellectual disability in humans. A hypomorphic mutation in the forkhead-associated domain of Unc-104, unc-104(bris), impairs active zone maturation resulting in an increased fraction of post-synaptic glutamate receptor fields that lack the active zone scaffolding protein Bruchpilot...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28315862/the-evolving-role-of-rituximab-in-adult-minimal-change-glomerulopathy
#2
Landon C Brown, Meghan A Jobson, Fernanda Payan Schober, Emily H Chang, Ronald J Falk, Patrick H Nachman, William F Pendergraft
BACKGROUND: Minimal-change glomerulopathy is defined histologically by the presence of normal glomeruli on light microscopy and diffuse podocyte effacement on electron microscopy. Although effective in children, corticosteroid treatment in adults is more variable and time to response can be prolonged. Data to support rituximab use in adults with corticosteroid-dependent or resistant minimal-change glomerulopathy are limited. Here, we describe the clinical course of adults with corticosteroid-dependent or -resistant minimal-change glomerulopathy who received rituximab...
March 18, 2017: American Journal of Nephrology
https://www.readbyqxmd.com/read/28315811/variant-two-stage-ileal-pouch-anal-anastomosis-an-innovative-and-effective-alternative-to-standard-resection-in-ulcerative-colitis
#3
Jennifer Samples, Krista Evans, Nicole Chaumont, Paula Strassle, Timothy Sadiq, Mark Koruda
BACKGROUND: Ulcerative colitis patients have been historically treated with standard single, two and three stage operative approaches. We perform a variant two-stage procedure beginning with total abdominal colectomy and end ileostomy followed by completion proctectomy and ileal pouch-anal anastomosis without a diverting loop ileostomy. The present study evaluates the effectiveness of this innovative alternative. STUDY DESIGN: Patients with ulcerative colitis admitted to UNC Hospital between 2003 and 2010 for IPAA were eligible for inclusion...
January 28, 2017: Journal of the American College of Surgeons
https://www.readbyqxmd.com/read/28292700/canonical-and-noncanonical-functions-of-ulk-atg1
#4
REVIEW
Bo Wang, Mondira Kundu
Mammalian Unc-51-like kinases 1 and 2 (ULK1 and ULK2) belong to the ULK/Atg1 family of serine/threonine kinases, which are conserved from yeast to mammals. Although ULK/Atg1 is best known for regulating flux through the autophagy pathway, it has evolutionarily conserved noncanonical functions in protein trafficking that are essential for maintaining cellular homeostasis. As a direct target of energy- and nutrient-sensing kinases, ULK/Atg1 is positioned to regulate the distribution and use of cellular resources in response to metabolic cues...
March 11, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/28291263/circumcision-does-not-alter-long-term-glucocorticoids-accumulation-or-psychological-effects-associated-with-trauma-and-stressor-related-disorders
#5
E Ullmann, J Licinio, A Barthel, K Petrowski, B Oratovski, T Stalder, C Kirschbaum, S R Bornstein
Male infants and boys through early adolescence can undergo circumcision either for the sake of upholding religious traditions or for medical reasons. According to both, Jewish as well as Islamic tenets, circumcision is a religious rite symbolizing the bond with God. The World Health Organization (WHO), the United Nations Council (UNC) as well as the American Academy of Pediatrics (AAP), and the Centers for Disease Control and Prevention (CDC) strongly recommend circumcision to promote hygiene and prevent disease...
March 14, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28282258/wnk1-is-an-unexpected-autophagy-inhibitor
#6
Sachith Gallolu Kankanamalage, A-Young Lee, Chonlarat Wichaidit, Andres Lorente-Rodriguez, Akansha M Shah, Steve Stippec, Angelique W Whitehurst, Melanie H Cobb
Autophagy is a cellular degradation pathway that is essential to maintain cellular physiology, and deregulation of autophagy leads to multiple diseases in humans. In a recent study, we discovered that the protein kinase WNK1 (WNK lysine deficient protein kinase 1) is an inhibitor of autophagy. The loss of WNK1 increases both basal and starvation-induced autophagy. In addition, the depletion of WNK1 increases the activation of the class III phosphatidylinositol 3-kinase (PtdIns3K) complex, which is required to induce autophagy...
February 15, 2017: Autophagy
https://www.readbyqxmd.com/read/28274987/the-university-of-north-carolina-medical-center-pharmacy-resident-leadership-certificate-program
#7
Kayley Lyons, Danielle Griggs, Rachel Lebovic, Mary E Roth, David A South, Chad Hatfield
PURPOSE: The development and implementation of a certificate program for pharmacy residents are described. SUMMARY: University of North Carolina (UNC) Medical Center met the call for increased efforts in the area of pharmacy residency leadership training through the design, implementation, and evaluation of a leadership certificate program. The purpose of the UNC certificate program is to develop leaders who will serve others, improve their communities, and advance the profession...
March 15, 2017: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/28258184/germ-granules-prevent-accumulation-of-somatic-transcripts-in-the-adult-caenorhabditis-elegans-germline
#8
Andrew Kekūpaʻa Knutson, Thea Egelhofer, Andreas Rechtsteiner, Susan Strome
The germ cells of multicellular organisms protect their developmental potential through specialized mechanisms. A shared feature of germ cells from worms to humans is the presence of non-membrane-bound ribonucleoprotein organelles called germ granules. Depletion of germ granules in Caenorhabditis elegans (i.e., P granules) leads to sterility and in some germlines expression of the neuronal transgene unc-119::gfp and the muscle myosin MYO-3. Thus, P granules are hypothesized to maintain germ cell totipotency by preventing somatic development, although the mechanism by which P granules carry out this function is unknown...
March 3, 2017: Genetics
https://www.readbyqxmd.com/read/28253968/study-of-ulk1-catalytic-activity-and-its-regulation
#9
B Stork, J Dengjel
During the last decade, the molecular mechanisms controlling the initiation of (macro-)autophagy have been extensively studied. Two macromolecular kinase complexes are central for the initiation of autophagy: the protein kinase unc-51-like kinase 1 (ULK1) complex and the lipid kinase VPS34/Beclin 1 complex. The serine/threonine kinase ULK1 represents the mammalian ortholog of yeast autophagy-related (Atg) protein 1 (Atg1). ULK1 is regulated by upstream nutrient- and energy-sensing kinases, and transmits these signals to the core autophagic machinery...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28246360/multiple-histone-lysine-methyltransferases-are-required-for-the-establishment-and-maintenance-of-hiv-1-latency
#10
Kien Nguyen, Biswajit Das, Curtis Dobrowolski, Jonathan Karn
We showed previously that the histone lysine methyltransferase (HKMT) H3K27me3 (EZH2) is the catalytic subunit of Polycomb repressive complex 2 (PRC2) and is required for the maintenance of HIV-1 latency in Jurkat T cells. Here we show, by using chromatin immunoprecipitation experiments, that both PRC2 and euchromatic histone-lysine N-methyltransferase 2 (EHMT2), the G9a H3K9me2-3 methyltransferase, are highly enriched at the proviral 5' long terminal repeat (LTR) and rapidly displaced upon proviral reactivation...
February 28, 2017: MBio
https://www.readbyqxmd.com/read/28225043/prevention-of-tumorigenesis-in-mice-by-exercise-is-dependent-on-strain-background-and-timing-relative-to-carcinogen-exposure
#11
Scott A Kelly, Liyang Zhao, Kuo-Chen Jung, Kunjie Hua, David W Threadgill, Yunjung Kim, Fernando Pardo Manuel de Villena, Daniel Pomp
Among cancer diagnoses, colorectal cancer (CRC) is prevalent, with a lifetime risk of developing CRC being approximately 5%. Population variation surrounding the mean risk of developing CRCs has been associated with both inter-individual differences in genomic architecture and environmental exposures. Decreased risk of CRC has been associated with physical activity, but protective responses are variable. Here, we utilized a series of experiments to examine the effects of genetic background (strain), voluntary exercise (wheel running), and their interaction on azoxymethane (AOM)-induced intestinal tumor number and size in mice...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28210206/the-unc-wisconsin-rhesus-macaque-neurodevelopment-database-a-structural-mri-and-dti-database-of-early-postnatal-development
#12
Jeffrey T Young, Yundi Shi, Marc Niethammer, Michael Grauer, Christopher L Coe, Gabriele R Lubach, Bradley Davis, Francois Budin, Rebecca C Knickmeyer, Andrew L Alexander, Martin A Styner
Rhesus macaques are commonly used as a translational animal model in neuroimaging and neurodevelopmental research. In this report, we present longitudinal data from both structural and diffusion MRI images generated on a cohort of 34 typically developing monkeys from 2 weeks to 36 months of age. All images have been manually skull stripped and are being made freely available via an online repository for use by the research community.
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28198711/longitudinal-opioid-use-among-hiv-infected-patients-2000-to-2014
#13
Laurence Brunet, Sonia Napravnik, Amy D Heine, Peter A Leone, Joseph J Eron
Longitudinal opioid prescription use is unknown among HIV-infected patients. Group-based trajectory modeling followed by multinomial logistic regression was used to identify distinct trajectories and their association with baseline characteristics among 1239 HIV-infected UNC CFAR HIV Clinical Cohort participants, 2000-2014. Three trajectories were identified: 1) 72% never/sporadic opioid use (referent group), 2) 11% episodic use (associated with female sex, depression, drug-related diagnoses, antiretroviral therapy use and undetectable HIV RNA), and 3) 16% chronic use (associated with older age, female sex and mental health diagnoses)...
February 14, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28196860/the-nclx-type-na-ca-2-exchanger-ncx-9-is-required-for-patterning-of-neural-circuits-in-caenorhabditis-elegans
#14
Vishal Sharma, Soumitra Roy, Israel Sekler, Damien M O'Halloran
NCLX is a Na(+)/Ca(2+) exchanger that uses energy stored in the transmembrane sodium gradient to facilitate the exchange of sodium ions for ionic calcium. Mammals have a single NCLX, which has been shown to function primarily at the mitochondrion and is an important regulator of neuronal physiology by contributing to neurotransmission and synaptic plasticity. The role of NCLX in developmental cell patterning, for example, in neural circuits, is largely unknown. Here we describe a novel role for the Caenorhabditis elegans NCLX-type protein, NCX-9, in neural circuit formation...
February 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28196472/premeta-a-tool-to-facilitate-meta-analysis-of-rare-variant-associations
#15
Zheng-Zheng Tang, Paul Bunn, Ran Tao, Zhouwen Liu, Dan-Yu Lin
BACKGROUND: Meta-analysis is essential to the discovery of rare variants that influence complex diseases and traits. Four major software packages, namely MASS, MetaSKAT, RAREMETAL, and seqMeta, have been developed to perform meta-analysis of rare-variant associations. These packages first generate summary statistics for each study and then perform the meta-analysis by combining the summary statistics. Because of incompatible file formats and non-equivalent summary statistics, the output files from the study-level analysis of one package cannot be directly used to perform meta-analysis in another package...
February 14, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28184925/inhibiting-plk1-induces-autophagy-of-acute-myeloid-leukemia-cells-via-mammalian-target-of-rapamycin-pathway-dephosphorylation
#16
Yan-Fang Tao, Zhi-Heng Li, Wei-Wei Du, Li-Xiao Xu, Jun-Li Ren, Xiao-Lu Li, Fang Fang, Yi Xie, Mei Li, Guang-Hui Qian, Yan-Hong Li, Yi-Ping Li, Gang Li, Yi Wu, Xing Feng, Jian Wang, Wei-Qi He, Shao-Yan Hu, Jun Lu, Jian Pan
Decreased autophagy is accompanied by the development of a myeloproliferative state or acute myeloid leukemia (AML). AML cells are often sensitive to autophagy‑inducing stimuli, prompting the idea that targeting autophagy can be useful in AML cytotoxic therapy. AML NB4 cells overexpressing microtubule-associated protein 1 light chain 3-green fluorescent protein were screened with 69 inhibitors to analyze autophagy activity. AML cells were treated with the polo-like kinase 1 (PLK1) inhibitors RO3280 and BI2536 before autophagy analysis...
March 2017: Oncology Reports
https://www.readbyqxmd.com/read/28165887/a-small-molecule-activator-induces-ulk1-modulating-autophagy-associated-cell-death-in-triple-negative-breast-cancer
#17
Liang Ouyang, Lan Zhang, Leilei Fu, Bo Liu
ULK1 (unc-51 like autophagy activating kinase 1) is well known to be required to initiate the macroautophagy/autophagy process, and thus activation of ULK1-modulating autophagy/autophagy-associated cell death (ACD) may be a possible therapeutic strategy in triple negative breast cancer (TNBC). Here, our integrated The Cancer Genome Atlas (TCGA) dataset, tissue microarray-based analyses and multiple biological evaluations together demonstrate a new small-molecule activator of ULK1 for better understanding of how ULK1, the mammalian homolog of yeast Atg1, as a potential drug target can regulate ACD by the ULK complex (ULK1-ATG13-RB1CC1/FIP200-ATG101), as well as other possible ULK1 interactors, including ATF3, RAD21 and CASP3/caspase3 in TNBC...
February 6, 2017: Autophagy
https://www.readbyqxmd.com/read/28162892/fast-camp-modulation-of-neurotransmission-via-neuropeptide-signals-and-vesicle-loading
#18
Wagner Steuer Costa, Szi-Chieh Yu, Jana F Liewald, Alexander Gottschalk
Cyclic AMP (cAMP) signaling augments synaptic transmission, but because many targets of cAMP and protein kinase A (PKA) may be involved, mechanisms underlying this pathway remain unclear. To probe this mechanism, we used optogenetic stimulation of cAMP signaling by Beggiatoa-photoactivated adenylyl cyclase (bPAC) in Caenorhabditis elegans motor neurons. Behavioral, electron microscopy (EM), and electrophysiology analyses revealed cAMP effects on both the rate and on quantal size of transmitter release and led to the identification of a neuropeptidergic pathway affecting quantal size...
February 20, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28161700/clinical-features-and-outcomes-of-a-racially-diverse-population-with-fibrillary-glomerulonephritis
#19
Fernanda Payan Schober, Meghan A Jobson, Caroline J Poulton, Harsharan K Singh, Volker Nickeleit, Ronald J Falk, J Charles Jennette, Patrick H Nachman, William F Pendergraft Iii
BACKGROUND: Fibrillary glomerulonephritis is characterized by randomly arranged fibrils, approximately 20 nm in diameter by electron microscopy. Patients present with proteinuria, hematuria and kidney insufficiency, and about half of the reported patients progress to end-stage kidney disease within 4 years. The dependence of patient characteristics and outcomes on race has not been explored. In this study, we describe a cohort of patients with fibrillary glomerulonephritis and compare their clinical characteristics and outcomes with those of patients previously described...
2017: American Journal of Nephrology
https://www.readbyqxmd.com/read/28160489/sec16-in-conventional-and-unconventional-exocytosis-working-at-the-interface-of-membrane-traffic-and-secretory-autophagy
#20
REVIEW
Bor Luen Tang
Sec16 is classically perceived to be a scaffolding protein localized to the transitional endoplasmic reticulum (tER) or the ER exit sites (ERES), and has a conserved function in facilitating coat protein II (COPII) complex-mediated ER exit. Recent findings have however pointed towards a role for Sec16 in unconventional exocytosis of certain membrane proteins, such as the Cystic fibrosis transmembrane conductance regulator (CFTR) in mammalian cells, and possibly also α-integrin in certain contexts of Drosophila development...
February 4, 2017: Journal of Cellular Physiology
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