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https://www.readbyqxmd.com/read/28919893/ripk3-fas-associated-death-domain-axis-regulates-pulmonary-immunopathology-to-cryptococcal-infection-independent-of-necroptosis
#1
Zhenzong Fa, Qun Xie, Wei Fang, Haibing Zhang, Haiwei Zhang, Jintao Xu, Weihua Pan, Jinhua Xu, Michal A Olszewski, Xiaoming Deng, Wanqing Liao
Fas-associated death domain (FADD) and receptor interacting protein kinase 3 (RIPK3) are multifunctional regulators of cell death and immune response. Using a mouse model of cryptococcal infection, the roles of FADD and RIPK3 in anti-cryptococcal defense were investigated. Deletion of RIPK3 alone led to increased inflammatory cytokine production in the Cryptococcus neoformans-infected lungs, but in combination with FADD deletion, it led to a robust Th1-biased response with M1-biased macrophage activation. Rather than being protective, these responses led to paradoxical C...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28904202/discrete-dynamical-modeling-of-influenza-infection-suggests-age-dependent-differences-in-immunity
#2
Ericka Keef, Li Ang Zhang, David Swigon, Alisa Urbano, G Bard Ermentrout, Michael Matuszewski, Franklin R Toapanta, Ted M Ross, Robert S Parker, Gilles Clermont
Immunosenescence, an age-related decline in immune function, is a major contributor to morbidity and mortality in the elderly. Older hosts exhibit delayed onset of immunity and prolonged inflammation after an infection, leading to excess damage and greater likelihood of death. Our study applies a rule-based model to infer which components of immune response are most changed in an aged host. Two groups of BALB/c mice (age 12-16 wks and 72-76 wks) were infected at 2 inocula: a survivable 50 PFU dose and a lethal 500 PFU dose...
September 13, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28899351/association-of-plasma-potassium-with-mortality-and-end-stage-kidney-disease-in-patients-with-chronic-kidney-disease-under-nephrologist-care-the-nephrotest-study
#3
Sandra Wagner, Marie Metzger, Martin Flamant, Pascal Houillier, Jean-Philippe Haymann, François Vrtovsnik, Eric Thervet, Jean-Jacques Boffa, Ziad A Massy, Bénédicte Stengel, Patrick Rossignol
BACKGROUND: Low and high blood potassium levels are common and were both associated with poor outcomes in patients with chronic kidney disease (CKD). Whether such relationships may be altered in CKD patients receiving optimized nephrologist care is unknown. METHODS: NephroTest is a hospital-based prospective cohort study that enrolled 2078 nondialysis patients (mean age: 59 ± 15 years, 66% men) in CKD stages 1 to 5 who underwent repeated extensive renal tests including plasma potassium (PK) and glomerular filtration rate (GFR) measured (mGFR) by (51)Cr-EDTA renal clearance...
September 12, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28894449/type-i-interferon-induced-by-streptococcus-suis-serotype-2-is-strain-dependent-and-may-be-beneficial-for-host-survival
#4
Jean-Philippe Auger, Agustina Santinón, David Roy, Karen Mossman, Jianguo Xu, Mariela Segura, Marcelo Gottschalk
Streptococcus suis serotype 2 is an important porcine bacterial pathogen and emerging zoonotic agent mainly responsible for sudden death, septic shock, and meningitis, with exacerbated inflammation being a hallmark of the infection. However, serotype 2 strains are genotypically and phenotypically heterogeneous, being composed of a multitude of sequence types (STs) whose virulence greatly varies: the virulent ST1 (Eurasia), highly virulent ST7 (responsible for the human outbreaks in China), and intermediate virulent ST25 (North America) are the most important worldwide...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28894089/heparan-sulfate-proteoglycans-present-pcsk9-to-the-ldl-receptor
#5
Camilla Gustafsen, Ditte Olsen, Joachim Vilstrup, Signe Lund, Anika Reinhardt, Niels Wellner, Torben Larsen, Christian B F Andersen, Kathrin Weyer, Jin-Ping Li, Peter H Seeberger, Søren Thirup, Peder Madsen, Simon Glerup
Coronary artery disease is the main cause of death worldwide and accelerated by increased plasma levels of cholesterol-rich low-density lipoprotein particles (LDL). Circulating PCSK9 contributes to coronary artery disease by inducing lysosomal degradation of the LDL receptor (LDLR) in the liver and thereby reducing LDL clearance. Here, we show that liver heparan sulfate proteoglycans are PCSK9 receptors and essential for PCSK9-induced LDLR degradation. The heparan sulfate-binding site is located in the PCSK9 prodomain and formed by surface-exposed basic residues interacting with trisulfated heparan sulfate disaccharide repeats...
September 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/28889265/manganese-and-the-insulin-igf-signaling-network-in-huntington-s-disease-and-other-neurodegenerative-disorders
#6
Miles R Bryan, Aaron B Bowman
Huntington's disease (HD) is an autosomal dominant neurodegenerative disease resulting in motor impairment and death in patients. Recently, several studies have demonstrated insulin or insulin-like growth factor (IGF) treatment in models of HD, resulting in potent amelioration of HD phenotypes via modulation of the PI3K/AKT/mTOR pathways. Administration of IGF and insulin can rescue microtubule transport, metabolic function, and autophagy defects, resulting in clearance of Huntingtin (HTT) aggregates, restoration of mitochondrial function, amelioration of motor abnormalities, and enhanced survival...
2017: Advances in Neurobiology
https://www.readbyqxmd.com/read/28883073/sterilizing-immunity-in-the-lung-relies-on-targeting-fungal-apoptosis-like-programmed-cell-death
#7
Neta Shlezinger, Henriette Irmer, Sourabh Dhingra, Sarah R Beattie, Robert A Cramer, Gerhard H Braus, Amir Sharon, Tobias M Hohl
Humans inhale mold conidia daily and typically experience lifelong asymptomatic clearance. Conidial germination into tissue-invasive hyphae can occur in individuals with defects in myeloid function, although the mechanism of myeloid cell-mediated immune surveillance remains unclear. By monitoring fungal physiology in vivo, we demonstrate that lung neutrophils trigger programmed cell death with apoptosis-like features in Aspergillus fumigatus conidia, the most prevalent human mold pathogen. An antiapoptotic protein, AfBIR1, opposes this process by inhibiting fungal caspase activation and DNA fragmentation in the murine lung...
September 8, 2017: Science
https://www.readbyqxmd.com/read/28883016/mitochondrial-dynamics-in-parkinson-s-disease-a-role-for-%C3%AE-synuclein
#8
REVIEW
Victorio M Pozo Devoto, Tomas L Falzone
The distinctive pathological hallmarks of Parkinson's disease are the progressive death of dopaminergic neurons and the intracellular accumulation of Lewy bodies enriched in α-synuclein protein. Several lines of evidence from the study of sporadic, familial and pharmacologically induced forms of human Parkinson's disease also suggest that mitochondrial dysfunction plays an important role in disease progression. Although many functions have been proposed for α-synuclein, emerging data from human and animal models of Parkinson's disease highlight a role for α-synuclein in the control of neuronal mitochondrial dynamics...
September 1, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28878781/calreticulin-release-at-an-early-stage-of-death-modulates-the-clearance-by-macrophages-of-apoptotic-cells
#9
Rim Osman, Pascale Tacnet-Delorme, Jean-Philippe Kleman, Arnaud Millet, Philippe Frachet
Calreticulin (CRT) is a well-known "eat-me" signal harbored by dying cells participating in their recognition by phagocytes. CRT is also recognized to deeply impact the immune response to altered self-cells. In this study, we focus on the role of the newly exposed CRT following cell death induction. We show that if CRT increases at the outer face of the plasma membrane and is well recognized by C1q even when phosphatidylserine is not yet detected, CRT is also released in the surrounding milieu and is able to interact with phagocytes...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28878620/autophagy-dysregulation-in-als-when-protein-aggregates-get-out-of-hand
#10
REVIEW
Nandini Ramesh, Udai Bhan Pandey
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that results from the loss of upper and lower motor neurons. One of the key pathological hallmarks in diseased neurons is the mislocalization of disease-associated proteins and the formation of cytoplasmic aggregates of these proteins and their interactors due to defective protein quality control. This apparent imbalance in the cellular protein homeostasis could be a crucial factor in causing motor neuron death in the later stages of the disease in patients...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28877825/effectiveness-of-peritoneal-dialysis-in-treating-adult-end-stage-renal-disease-patients-with-polycystic-kidney-disease
#11
Ying Ma, Hai-Yun Wang, Zi-Juan Zhou, Yang Li, Wei Yang, Bing-Yan Liu, Jing-Hua Xia, Xue-Mei Li, Li-Meng Chen
Objective To observe the clinical characteristics,dialysis modalities,and outcomes of end stage renal disease(ESRD)patients with polycystic kidney disease(PKD)and to evaluate the feasibility of peritoneal dialysis in these population. Methods The clinical data of ESRD patient whose primary diagnosis was PKD in Peking Union Medical College Hospital were retrospectively collected from January 1993 to December 2015.PKD patients were divided into two groups according to dialysis modality,namely peritoneal dialysis group(PKD-PD)group and hemodialysis(PKD-HD)group...
August 20, 2017: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta Academiae Medicinae Sinicae
https://www.readbyqxmd.com/read/28874382/evaluation-of-the-innate-immune-modulator-acitretin-as-a-strategy-to-clear-the-hiv-reservoir
#12
Edurne Garcia-Vidal, Marc Castellví, Maria Pujantell, Roger Badia, Antoni Jou, Lucia Gomez, Teresa Puig, Bonaventura Clotet, Ester Ballana, Eva Riveira-Muñoz, José A Esté
The persistence of HIV despite suppressive antiretroviral therapy is a major roadblock to HIV eradication. Current strategies focused on inducing the expression of latent HIV fail to clear the persistent reservoir, prompting the development of new approaches for killing HIV+ cells. Recently, acitretin has been proposed as a pharmacological innate cellular-defense network enhancer that led to virus reactivation and preferential death of infected cells. We have evaluated the capacity of acitretin to reactivate and/or facilitate immune-mediated clearance of HIV+ cells...
September 5, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28866117/association-of-post-procedural-early-within-24h-increases-in-serum-creatinine-with-all-cause-mortality-after-coronary-angiography
#13
Xiao-Sheng Guo, Shi-Qun Chen, Chong-Yang Duan, Hua-Long Li, Wei-Jie Bei, Yong Liu, Ning Tan, Ping-Yan Chen, Ji-Yan Chen
BACKGROUND: The majority of patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI) are discharged early, with only early (within 24h) serum creatinine (SCr) data available without evidence of clinical prognosis. We aimed to systemically evaluate the association between post-procedural early increase in SCr and all-cause mortality following CAG. METHODS: We performed a retrospective sub-study analysis within a prospective observational study including 3091 consecutive patients with baseline and post-procedural early (within 24h) SCr data...
August 30, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28861421/the-role-of-reactive-oxygen-species-in-myocardial-redox-signaling-and-regulation
#14
REVIEW
Demetrios Moris, Michael Spartalis, Eleni Tzatzaki, Eleftherios Spartalis, Georgia-Sofia Karachaliou, Andreas S Triantafyllis, Georgios I Karaolanis, Diamantis I Tsilimigras, Stamatios Theocharis
Reactive oxygen species (ROS) are subcellular messengers in gene regulatory and signal transduction pathways. In pathological situations, ROS accumulate due to excessive production or insufficient degradation, leading to oxidative stress (OS). OS causes oxidation of DNA, membranes, cellular lipids, and proteins, impairing their normal function and leading ultimately to cell death. OS in the heart is increased in response to ischemia/reperfusion, hypertrophy, and heart failure. The concentration of ROS is determined by their rates of production and clearance by antioxidants...
August 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28853594/bone-metastases-of-the-hand
#15
G Morris, S Evans, J Stevenson, A Kotecha, M Parry, L Jeys, R Grimer
Introduction The aim of this study was to identify patients with malignant hand lesions, establish the proportions of those that were metastases and review their clinical course. Methods A retrospective search of a prospective tumour database was carried out to identify all patients treated at our unit with hand metastases. Patient demographics were recorded including site of primary malignancy, region of the hand involved, management of their metastasis and clinical outcome. Results Overall, 149 patients were identified with a malignant tumour of the hand...
September 2017: Annals of the Royal College of Surgeons of England
https://www.readbyqxmd.com/read/28852522/systematic-review-of-mixed-cryoglobulinemia-associated-with-hepatitis-e-virus-infection-association-or-causation
#16
REVIEW
Fateh Bazerbachi, Michael D Leise, Kymberly D Watt, M Hassan Murad, Larry J Prokop, Samir Haffar
Background and aim: Mixed cryoglobulinemia (MC) has been associated with several viral infections, and chronic hepatitis C is recognized as a major cause. MC associated with hepatitis E virus (HEV) has been described and little is known about this rare association. The aim of this study is to perform a systematic review of MC associated with HEV, and examine the presence of a causal relationship. Methods: An experienced librarian conducted a search of databases from each database's inception to 12 December 2016 based on a priori criteria...
August 2017: Gastroenterology Report
https://www.readbyqxmd.com/read/28852057/placental-dysfunction-underlies-increased-risk-of-fetal-growth-restriction-and-stillbirth-in-advanced-maternal-age-women
#17
Samantha C Lean, Alexander E P Heazell, Mark R Dilworth, Tracey A Mills, Rebecca L Jones
Pregnancies in women of advanced maternal age (AMA) are susceptible to fetal growth restriction (FGR) and stillbirth. We hypothesised that maternal ageing is associated with utero-placental dysfunction, predisposing to adverse fetal outcomes. Women of AMA (≥35 years) and young controls (20-30 years) with uncomplicated pregnancies were studied. Placentas from AMA women exhibited increased syncytial nuclear aggregates and decreased proliferation, and had increased amino acid transporter activity. Chorionic plate and myometrial artery relaxation was increased compared to controls...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28851711/perturbing-phosphoinositide-homeostasis-oppositely-affects-vascular-differentiation-in-arabidopsis-thaliana-roots
#18
Bojan Gujas, Tiago M D Cruz, Elizabeth Kastanaki, Joop E M Vermeer, Teun Munnik, Antia Rodriguez-Villalon
The plant vascular network consists of specialized phloem and xylem elements that undergo two distinct morphogenetic developmental programs to become transport-functional units. While vacuolar rupture is a determinant step in protoxylem differentiation, protophloem elements never form a big central vacuole. Here we show that a genetic disturbance of phosphatidylinositol 4,5-bis-phosphate [PtdIns(4,5)P2] homeostasis rewires cell trafficking towards the vacuole in Arabidopsis thaliana roots. Consequently, an enhanced phosphoinositide-mediated vacuolar biogenesis correlate with premature programmed cell death (PCD) and secondary cell wall elaboration in xylem cells...
August 29, 2017: Development
https://www.readbyqxmd.com/read/28834546/pharmacokinetics-and-safety-of-a-single-oral-dose-of-mirogabalin-in-japanese-subjects-with-varying-degrees-of-renal-impairment
#19
Manabu Kato, Naoyuki Tajima, Takako Shimizu, Masahiro Sugihara, Kenichi Furihata, Kazuhiro Harada, Hitoshi Ishizuka
Mirogabalin (DS-5565) is a novel preferentially selective α2 δ-1 ligand being developed for the treatment of diabetic peripheral neuropathic pain and postherpetic neuralgia. The current multicenter open-label study determined the effect of varying degrees of renal impairment on the pharmacokinetics and safety of a single dose of mirogabalin 5 mg in Japanese subjects. A total of 30 subjects (6 subjects per renal function category [normal, mild, moderate, or severe impairment; and end-stage renal disease (ESRD)]) were enrolled and completed the study...
August 23, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28833798/expressions-of-programmed-death-pd-1-and-pd-1-ligand-pd-l1-in-cervical-intraepithelial-neoplasia-and-cervical-squamous-cell-carcinomas-are-of-prognostic-value-and-associated-with-human-papillomavirus-status
#20
Wen Yang, Yan-Ping Lu, Yi-Zhou Yang, Jia-Rui Kang, Yi-Duo Jin, Hong-Wei Wang
AIM: The programmed death 1/programmed death 1 ligand (PD-1/PD-L1) pathway can decrease the immune clearance effects of antigen-presenting cells and T lymphocytes to promote immune evasion of cervical cancer cells. However, the effects of this pathway on cervical intraepithelial neoplasia (CIN) progression and squamous cell carcinoma (SCC) metastasis are not clear. We herein investigated whether human papillomavirus infection could affect PD-1 and PD-L1 expression in CIN, and whether their expression is associated with CIN progression and SCC metastasis...
August 17, 2017: Journal of Obstetrics and Gynaecology Research
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