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https://www.readbyqxmd.com/read/29787814/lipid-modified-cell-penetrating-peptide-based-self-assembly-micelles-for-co-delivery-of-narciclasine-and-siulk1-in-hepatocellular-carcinoma-therapy
#1
Xiaoyun Wang, Fengbo Wu, Guoyou Li, Nan Zhang, Xiangrong Song, Yu Zheng, Changyang Gong, Bo Han, Gu He
Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer, and one therapeutic approach is to target both the AMPK and autophagy pathways in order to synergistically promote programmed cell death. Here, a series of amphiphilic, lipid-modified cell-penetrating peptides were synthesized and allowed to self-assemble into micelles loaded with the AMPK activator narciclasine (Narc) and short interfering RNA targeting the unc-51-like kinase 1 (siULK1). The size of these micelles, their efficiency of transfection into cells, and their ability to release drug or siRNA cargo in vitro were pH-sensitive, such that drug release was facilitated in the acidic microenvironment of the tumor...
May 19, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29784905/northward-shift-of-the-agricultural-climate-zone-under-21-st-century-global-climate-change
#2
Myron King, Daniel Altdorff, Pengfei Li, Lakshman Galagedara, Joseph Holden, Adrian Unc
As agricultural regions are threatened by climate change, warming of high latitude regions and increasing food demands may lead to northward expansion of global agriculture. While socio-economic demands and edaphic conditions may govern the expansion, climate is a key limiting factor. Extant literature on future crop projections considers established agricultural regions and is mainly temperature based. We employed growing degree days (GDD), as the physiological link between temperature and crop growth, to assess the global northward shift of agricultural climate zones under 21st -century climate change...
May 21, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29784669/autophagy-cell-viability-and-chemo-resistance-are-regulated-by-mir-489-in-breast-cancer
#3
Hexin Chen, Mithil Soni, Yogin Patel, Eleni Markoutsa, Chunfa Jie, Shou Liu, Peisheng Xu
It is postulated that the complexity and heterogeneity in cancer may hinder most efforts that target a single pathway. Thus, discovery of novel therapeutic agents targeting multiple pathways, such as microRNAs (miRs), holds promise for future cancer therapy. One such miR, miR-489, is downregulated in majority of breast cancer cells and several drug-resistant breast cancer cell lines, but its role and underlying mechanism for tumor suppression and drug resistance needs further investigation. The current study identifies autophagy as a novel pathway targeted by miR-489 and reports Unc-51 like autophagy activating kinase 1 (ULK1) and lysosomal protein transmembrane 4 beta (LAPTM4B) to be direct targets of miR-489...
May 21, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29784083/a-homozygous-loss-of-function-camk2a-mutation-causes-growth-delay-frequent-seizures-and-severe-intellectual-disability
#4
Poh Hui Chia, Franklin Lei Zhong, Shinsuke Niwa, Carine Bonnard, Kagistia Hana Utami, Ruizhu Zeng, Hane Lee, Ascia Eskin, Stanley F Nelson, William H Xie, Samah Al-Tawalbeh, Mohammad El-Khateeb, Mohammad Shboul, Mahmoud A Pouladi, Mohammed Al-Raqad, Bruno Reversade
Calcium/calmodulin-dependent protein kinase II (CAMK2) plays fundamental roles in synaptic plasticity that underlies learning and memory. Here, we describe a new recessive neurodevelopmental syndrome with global developmental delay, seizures and intellectual disability. Using linkage analysis and exome sequencing, we found that this disease maps to chromosome 5q31.1-q34 and is caused by a biallelic germline mutation in CAMK2A . The missense mutation, p.His477Tyr is located in the CAMK2A association domain that is critical for its function and localization...
May 22, 2018: ELife
https://www.readbyqxmd.com/read/29768176/the-chaperone-unc93b1-regulates-toll-like-receptor-stability-independently-of-endosomal-tlr-transport
#5
Karin Pelka, Damien Bertheloot, Elisa Reimer, Kshiti Phulphagar, Susanne V Schmidt, Anette Christ, Rainer Stahl, Nicki Watson, Kensuke Miyake, Nir Hacohen, Albert Haas, Melanie M Brinkmann, Ann Marshak-Rothstein, Felix Meissner, Eicke Latz
Unc-93 homolog B1 (UNC93B1) is a key regulator of nucleic acid (NA)-sensing Toll-like receptors (TLRs). Loss of NA-sensing TLR responses in UNC93B1-deficient patients facilitates Herpes simplex virus type 1 (HSV-1) encephalitis. UNC93B1 is thought to guide NA-sensing TLRs from the endoplasmic reticulum (ER) to their respective endosomal signaling compartments and to guide the flagellin receptor TLR5 to the cell surface, raising the question of how UNC93B1 mediates differential TLR trafficking. Here, we report that UNC93B1 regulates a step upstream of the differential TLR trafficking process...
May 15, 2018: Immunity
https://www.readbyqxmd.com/read/29752434/activation-of-tgf-%C3%AE-activated-kinase-1-tak1-restricts-salmonella-typhimurium-growth-by-inducing-ampk-activation-and-autophagy
#6
Wei Liu, Yuanyuan Jiang, Jing Sun, Shizhong Geng, Zhiming Pan, Richard A Prinz, Chengming Wang, Jun Sun, Xinan Jiao, Xiulong Xu
Autophagy is a conserved cellular process that functions as a first-line defense to restrict the growth of invading parasitic bacteria. As an intracellular pathogen, Salmonella (S) Typhimurium invades host cells through two Type III secretion systems (T3SS) and resides in the Salmonella-containing vacuole (SCV). When the SCV membrane is perforated and ruptured by T3SS-1, a small portion of the Salmonella egresses from the SCV and replicates rapidly in the nutrient-rich cytosol. Cytosolic Salmonella and those residing in the membrane-damaged SCV are tagged by ubiquitination and marked for autophagy through the ubiquitin-binding adaptor proteins such as p62, NDP52, and optineurin...
May 11, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29750625/trends-and-characteristics-of-pediatric-dentistry-patients-treated-under-general-anesthesia
#7
Maxwell N Rudie, Michael M Milano, Michael W Roberts, Kimon Divaris
PURPOSE: The aims of this study were to describe the demographic characteristics of pediatric dentistry patients undergoing dental rehabilitation under general anesthesia (DRGA) at UNC-Chapel Hill during the last 13 years and identify factors associated with multiple (1 versus 2 or more) DRGA visits during that timeframe. STUDY DESIGN: Administrative claims data were used to identify children and adolescents (age <18 years) who underwent DRGA between 1/1/2002 and 12/31/2014 at the UNC Hospitals system...
May 11, 2018: Journal of Clinical Pediatric Dentistry
https://www.readbyqxmd.com/read/29749377/p2rx7-mapk1-2-sp1-axis-inhibits-mtor-independent-hspb1-mediated-astroglial-autophagy
#8
Ji-Eun Kim, Ah-Reum Ko, Hye-Won Hyun, Su-Ji Min, Tae-Cheon Kang
Recently, we have reported that heat shock protein B1 (HSPB1) and purinergic receptor P2X7 (P2RX7) are involved in astroglial autophagy (clasmatodendrosis), following status epilepticus (SE). However, the underlying mechanisms of astroglial autophagy have not been completely established. In the present study, we found that the lacking of P2rx7 led to prolonged astroglial HSPB1 induction due to impaired mitogen-activated protein kinase 1/2 (MAPK1/2)-mediated specificity protein 1 (SP1) phosphorylation, following kainic acid-induced SE...
May 10, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29748380/ccar-1-affects-hemidesmosome-biogenesis-by-regulating-unc-52-perlecan-alternative-splicing-in-the-c-elegans-epidermis
#9
Rong Fu, Yi Zhu, Xiaowan Jiang, Yuanbao Li, Ming Zhu, Mengqiu Dong, Zhaohui Huang, Chunxia Wang, Michel Labouesse, Huimin Zhang
Hemidesmosomes are epithelial-specific attachment structures that maintain tissue integrity and resist tension. Despite their importance, how hemidesmosomes are regulated at the post-transcriptional level is poorly understood. C. elegans hemidesmosomes (CeHDs) share similar structure and composition with their mammalian counterparts, making C. elegans an ideal model for studying hemidesmosomes. Here we focus on the transcription regulator CCAR-1, identified in a previous genetic screen searching for enhancers of mutations in the conserved hemidesmosome component, VAB-10A/Plectin...
May 10, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29747490/health-related-quality-of-life-perceived-social-support-and-depression-in-disease-free-survivors-who-underwent-curative-surgery-only-for-prostate-kidney-and-bladder-cancer-comparison-among-survivors-and-with-the-general-population
#10
Dong Wook Shin, Hyun Sik Park, Sang Hyub Lee, Seung Hyun Jeon, Seok Cho, Seok Ho Kang, Seung Chol Park, Jong Hyock Park, Jinsung Park
Purpose: The purpose of this study was to compare health-related quality of life (HRQoL) of disease-free prostate (PC), kidney (KC), and bladder cancer (BC) survivors with that of the general population. Materials and Methods: Our study included 331 urological cancer (UC) survivors (114 PC, 108 KC, and 109 BC) aged ≥ 50 years disease-free for at least 1 year after surgery. The control group included 1,177 subjects without a history of cancer. The HRQoL was assessed using the European Organization for Research and Treatment of Cancer QLQ-C30, the Duke-UNC Functional Social Support Questionnaire, and the Patient Health Questionnaire-9...
May 4, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/29746831/helicobacter-pylori-infection-modulates-host-cell-metabolism-through-vaca-dependent-inhibition-of-mtorc1
#11
Ik-Jung Kim, Jeongmin Lee, Seung J Oh, Mee-Sup Yoon, Sung-Soo Jang, Robin L Holland, Michael L Reno, Mohammed N Hamad, Tatsuya Maeda, Hee Jung Chung, Jie Chen, Steven R Blanke
Helicobacter pylori (Hp) vacuolating cytotoxin (VacA) is a bacterial exotoxin that enters host cells and induces mitochondrial dysfunction. However, the extent to which VacA-dependent mitochondrial perturbations affect overall cellular metabolism is poorly understood. We report that VacA perturbations in mitochondria are linked to alterations in cellular amino acid homeostasis, which results in the inhibition of mammalian target of rapamycin complex 1 (mTORC1) and subsequent autophagy. mTORC1, which regulates cellular metabolism during nutrient stress, is inhibited during Hp infection by a VacA-dependent mechanism...
May 9, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/29744478/relative-to-open-surgery-minimally-invasive-renal-and-ureteral-pediatric-surgery-offers-no-improvement-in-30-day-complications-yet-requires-longer-operative-time-data-from-the-national-surgical-quality-improvement-program-pediatrics
#12
Marc Colaco, Austin Hester, William Visser, Alison Rasper, Ryan Terlecki
Purpose: Performance of minimally-invasive surgery (MIS) is increasing relative to open surgery. We sought to compare the contemporary rates of short-term complications of open versus laparoscopic renal and ureteral surgery in pediatric patients. Materials and Methods: A retrospective cross-sectional analysis of the National Surgical Quality Improvement Program Pediatrics database was performed of all cases in 2014 identified using CPT procedure codes for nephrectomy, partial nephrectomy (PN), ureteroneocystostomy (UNC), and pyeloplasty, and reviewed for postoperative complications...
May 2018: Investigative and Clinical Urology
https://www.readbyqxmd.com/read/29742100/the-receptor-protein-tyrosine-phosphatase-clr-1-is-required-for-synaptic-partner-recognition
#13
Aruna Varshney, Kelli Benedetti, Katherine Watters, Raakhee Shankar, David Tatarakis, Doris Coto Villa, Khristina Magallanes, Venia Agenor, William Wung, Fatima Farah, Nebat Ali, Nghi Le, Jacqueline Pyle, Amber Farooqi, Zanett Kieu, Martina Bremer, Miri VanHoven
During neural circuit formation, most axons are guided to complex environments, coming into contact with multiple potential synaptic partners. However, it is critical that they recognize specific neurons with which to form synapses. Here, we utilize the split GFP-based marker Neuroligin-1 GFP Reconstitution Across Synaptic Partners (NLG-1 GRASP) to visualize specific synapses in live animals, and a circuit-specific behavioral assay to probe circuit function. We demonstrate that the receptor protein tyrosine phosphatase (RPTP) clr-1 is necessary for synaptic partner recognition (SPR) between the PHB sensory neurons and the AVA interneurons in C...
May 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29726613/the-novel-cyst-nematode-effector-protein-30d08-targets-host-nuclear-functions-to-alter-gene-expression-in-feeding-sites
#14
Anju Verma, Chris Lee, Stephanie Morriss, Fiona Odu, Charlotte Kenning, Nancy Rizzo, William G Spollen, Marriam Lin, Amanda G McRae, Scott A Givan, Tarek Hewezi, Richard Hussey, Eric L Davis, Thomas J Baum, Melissa G Mitchum
Cyst nematodes deliver effector proteins into host cells to manipulate cellular processes and establish a metabolically hyperactive feeding site. The novel 30D08 effector protein is produced in the dorsal gland of parasitic juveniles, but its function has remained unknown. We demonstrate that expression of 30D08 contributes to nematode parasitism, the protein is packaged into secretory granules and it is targeted to the plant nucleus where it interacts with SMU2 (homolog of suppressor of mec-8 and unc-52 2), an auxiliary spliceosomal protein...
May 4, 2018: New Phytologist
https://www.readbyqxmd.com/read/29719008/deciphering-the-molecular-determinants-of-cholinergic-anthelmintic-sensitivity-in-nematodes-when-novel-functional-validation-approaches-highlight-major-differences-between-the-model-caenorhabditis-elegans-and-parasitic-species
#15
Alexandra Blanchard, Fabrice Guégnard, Claude L Charvet, Anna Crisford, Elise Courtot, Christine Sauvé, Abdallah Harmache, Thomas Duguet, Vincent O'Connor, Philippe Castagnone-Sereno, Barbara Reaves, Adrian J Wolstenholme, Robin N Beech, Lindy Holden-Dye, Cedric Neveu
Cholinergic agonists such as levamisole and pyrantel are widely used as anthelmintics to treat parasitic nematode infestations. These drugs elicit spastic paralysis by activating acetylcholine receptors (AChRs) expressed in nematode body wall muscles. In the model nematode Caenorhabditis elegans, genetic screens led to the identification of five genes encoding levamisole-sensitive-AChR (L-AChR) subunits: unc-38, unc-63, unc-29, lev-1 and lev-8. These subunits form a functional L-AChR when heterologously expressed in Xenopus laevis oocytes...
May 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29713938/the-urgent-neurological-consultation-in-the-population-of-the-province-of-ferrara-italy
#16
Vittorio Govoni, Elena Della Coletta, Elisa Fallica, Edward Cesnik
In the province of Ferrara, Italy, the urgent neurological consultation (UNC) cases in the population correspond to the resident outpatients who undergo a UNC in the ER of the university hospital of Ferrara (UHFe). Thanks to this health organization a retrospective survey identified 612 UNC cases (range of age 7-102 years, median 67,5 years) in the study period giving a period prevalence rate of 173 per 100,000 (95% CI 159.3-187.3) which increased with age (χ2 for trend = 178.4 p < 0.001). The daily UNC cases (range 0-14, mean = 7...
May 1, 2018: Neurological Sciences
https://www.readbyqxmd.com/read/29709602/structure-dynamics-and-biochemical-characterization-of-adf-cofilin-twinstar-from-drosophila-melanogastor
#17
Vaibhav Kumar Shukla, Diva Maheshwari, Anupam Jain, Sarita Tripathi, Dinesh Kumar, Ashish Arora
BACKGROUND: Twinstar is an ADF/Cofilin family protein, which is expressed by the tsr gene in Drosophila melanogaster. Twinstar is one of the main regulators of actin cytoskeleton remodelling and is essential for vital cellular processes like cytokinesis and endocytosis. METHODS: We have characterized the structure and dynamics of Twinstar by solution NMR spectroscopy, the interaction of Twinstar with rabbit muscle actin by ITC, and biochemical activities of Twinstar through different biochemical assays using fluorescence spectroscopy and ultra-centrifugation...
April 27, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29708352/-anogenital-hpv-infection-as-the-potential-risk-factor-for-oropharyngeal-carcinoma
#18
Borek Sehnal, Tomáš Podlešák, Emanuela Kmoníčková, Monika Nipčová, Daniel Driák, Jiří Sláma, Michal Zikán
BACKGROUND: Human papillomavirus (HPV) can cause cervical, other genital, anal, head, and neck cancers. The incidence of oropharyngeal squamous cell carcinoma (OSCC), the head and neck cancer most commonly caused by HPV infection, is increasing. The prevalence of oral HPV infections is considerably lower than that of genital HPV infections; however, infection of both sites is strongly associated with sexual behavior. Although the natural histories of cervical and oral HPV infections do not markedly differ, the virus seems to rarely infect oral and genital sites simultaneously...
2018: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/29694889/pro-inflammation-associated-with-a-gain-of-function-mutation-r284s-in-the-innate-immune-sensor-sting
#19
Hiroyasu Konno, Ivan K Chinn, Diana Hong, Jordan S Orange, James R Lupski, Alejandra Mendoza, Luis A Pedroza, Glen N Barber
The cellular sensor stimulator of interferon genes (STING) initiates type I interferon (IFN) and cytokine production following association with cyclic dinucleotides (CDNs) generated from intracellular bacteria or via a cellular synthase, cGAS, after binding microbial or self-DNA. Although essential for protecting the host against infection, unscheduled STING signaling is now known to be responsible for a variety of autoinflammatory disorders. Here, we report a gain-of-function mutation in STING (R284S), isolated from a patient who did not require CDNs to augment activity and who manifested a constitutively active phenotype...
April 24, 2018: Cell Reports
https://www.readbyqxmd.com/read/29694233/functional-features-of-the-finger-domain-of-deg-enac-channels-mec-4-and-unc-8
#20
Cristina Matthewman, Christina K Johnson, David M Miller Iii, Laura Bianchi
UNC-8 and MEC-4 are two members of the DEG/ENaC family of voltage-independent Na+ channels that share a high degree of sequence homology and functional similarity. For example, both can be hyperactivated by genetic mutations (UNC-8(d) and MEC-4(d)) that induce neuronal death by necrosis. Both depend in vivo on chaperone protein MEC-6 for function, as demonstrated by the finding that neuronal death induced by hyperactive UNC-8 and MEC-4 channels is prevented by null mutations in mec-6. UNC-8 and MEC-4 differ functionally in three major ways: 1) MEC-4 is calcium permeable whereas UNC-8 is not; 2) UNC-8, but not MEC-4, is blocked by extracellular calcium and magnesium in the micromolar range; 3) MEC-6 increases the number of MEC-4 channels at the cell surface in oocytes but does not have this effect on UNC-8...
April 25, 2018: American Journal of Physiology. Cell Physiology
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