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https://www.readbyqxmd.com/read/28640966/linking-the-degree-of-virilization-in-females-with-congenital-adrenal-hyperplasia-to-genotype
#1
Semyon Gurgov, Kerlly J Bernabé, John Stites, Christopher M Cunniff, Karen Lin-Su, Diane Felsen, Maria I New, Dix P Poppas
Mutations of CYP21A2 variably decrease 21-hydroxylase activity and result in a spectrum of disease expressions in patients with congenital adrenal hyperplasia (CAH). We examined the association between CYP21A2 mutations and virilization (Prader score) in females with CAH. The study population included 187 CAH females with fully characterized CYP21A2 mutations. One hundred fifty-eight patients were sorted into groups by expected enzyme activity (percent of normal activity) of the less severely affected allele: (A) null, 0%; (B) I2G, 1%; (C) I172N, 2%; and (D) V281L, >2%...
June 22, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28640918/identifying-key-demographic-parameters-of-a-small-island-associated-population-of-indo-pacific-bottlenose-dolphins-reunion-indian-ocean
#2
Violaine Dulau, Vanessa Estrade, Jacques Fayan
Photo-identification surveys of Indo-Pacific bottlenose dolphins were conducted from 2009 to 2014 off Reunion Island (55°E33'/21°S07'), in the Indian Ocean. Robust Design models were applied to produce the most reliable estimate of population abundance and survival rate, while accounting for temporary emigration from the survey area (west coast). The sampling scheme consisted of a five-month (June-October) sampling period in each year of the study. The overall population size at Reunion was estimated to be 72 individuals (SE = 6...
2017: PloS One
https://www.readbyqxmd.com/read/28637716/modulation-of-plasma-metabolite-biomarkers-of-mapk-pathway-with-the-mek-inhibitor-ro4987655-pharmacodynamic-and-predictive-potential-in-metastatic-melanoma
#3
Joo Ern Ang, Akos Pal, Yasmin J Asad, Alan T Henley, Melanie Valenti, Gary Box, Alexis de Haven Brandon, Victoria Revell, Debra J Skene, Miro Venturi, Ruediger Rueger, Valerie Meresse, Suzanne A Eccles, Johann S de Bono, Stanley B Kaye, Paul Workman, Udai Banerji, Florence I Raynaud
<p>MAPK pathway activation is frequently observed in human malignancies, including melanoma, and is associated with sensitivity to MEK inhibition and changes in cellular metabolism. Using quantitative mass spectrometry-based metabolomics, we identified in preclinical models 21 plasma metabolites including amino acids, propionylcarnitine, phosphatidylcholines and sphingomyelins that were significantly altered in two B-RAF mutant melanoma xenografts and that were reversed following a single dose of the potent and selective MEK inhibitor RO4987655...
June 21, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28637009/jagged-2-jag2-enhances-tumorigenicity-and-chemoresistance-of-colorectal-cancer-cells
#4
Vivek Vaish, Joohwee Kim, Minsub Shim
Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality. Recent studies have stated that NOTCH signaling plays an important role in the development and progression of CRC. However, the role of Jagged-2 (JAG2), one of the NOTCH ligands, has not been delineated in colorectal tumorigenesis and drug resistance. In the present study, we have examined the impact of targeting JAG2 on CRC cells. Among all the members of NOTCH ligands, only the expression of JAG2 was found up-regulated in the intestinal tumors of ApcMin/+ mice as compared to the nearby normal mucosa...
June 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28635948/munc13-1-and-munc18-1-together-prevent-nsf-dependent-de-priming-of-synaptic-vesicles
#5
Enqi He, Keimpe Wierda, Rhode van Westen, Jurjen H Broeke, Ruud F Toonen, L Niels Cornelisse, Matthijs Verhage
Synaptic transmission requires a stable pool of release-ready (primed) vesicles. Here we show that two molecules involved in SNARE-complex assembly, Munc13-1 and Munc18-1, together stabilize release-ready vesicles by preventing de-priming. Replacing neuronal Munc18-1 by a non-neuronal isoform Munc18-2 (Munc18-1/2SWAP) supports activity-dependent priming, but primed vesicles fall back into a non-releasable state (de-prime) within seconds. Munc13-1 deficiency produces a similar defect. Inhibitors of N-ethylmaleimide sensitive factor (NSF), N-ethylmaleimide (NEM) or interfering peptides, prevent de-priming in munc18-1/2SWAP or munc13-1 null synapses, but not in CAPS-1/2 null, another priming-deficient mutant...
June 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28635126/reinterpreting-maximum-entropy-in-ecology-a-null-hypothesis-constrained-by-ecological-mechanism
#6
James P O'Dwyer, Andrew Rominger, Xiao Xiao
Simplified mechanistic models in ecology have been criticised for the fact that a good fit to data does not imply the mechanism is true: pattern does not equal process. In parallel, the maximum entropy principle (MaxEnt) has been applied in ecology to make predictions constrained by just a handful of state variables, like total abundance or species richness. But an outstanding question remains: what principle tells us which state variables to constrain? Here we attempt to solve both problems simultaneously, by translating a given set of mechanisms into the state variables to be used in MaxEnt, and then using this MaxEnt theory as a null model against which to compare mechanistic predictions...
July 2017: Ecology Letters
https://www.readbyqxmd.com/read/28634550/sortilin-related-receptor-expression-in-human-neural-stem-cells-derived-from-alzheimer-s-disease-patients-carrying-the-apoe-epsilon-4-allele
#7
Alen Zollo, Zoe Allen, Helle F Rasmussen, Filomena Iannuzzi, Yichen Shi, Agnete Larsen, Thorsten J Maier, Carmela Matrone
Alzheimer's disease (AD) is the most common form of dementia in the elderly; important risk factors are old age and inheritance of the apolipoprotein E4 (APOE4) allele. Changes in amyloid precursor protein (APP) binding, trafficking, and sorting may be important AD causative factors. Secretase-mediated APP cleavage produces neurotoxic amyloid-beta (Aβ) peptides, which form lethal deposits in the brain. In vivo and in vitro studies have implicated sortilin-related receptor (SORL1) as an important factor in APP trafficking and processing...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/28634273/the-c-elegans-vapb-homolog-vpr-1-is-a-permissive-signal-for-gonad-development
#8
Pauline A Cottee, Tim Cole, Jessica Schultz, Hieu D Hoang, Jack Vibbert, Sung Min Han, Michael A Miller
VAMP/synaptobrevin-associated proteins (VAPs) contain an N-terminal major sperm protein domain (MSPd) that is associated with amyotrophic lateral sclerosis. VAPs have an intracellular housekeeping function, as well as an extracellular signaling function mediated by the secreted MSPd. Here we show that the C. elegans VAP homolog VPR-1 is essential for gonad development. vpr-1 null mutants are maternal effect sterile due to arrested gonadogenesis following embryo hatching. Somatic gonadal precursor cells and germ cells fail to proliferate fully and complete their respective differentiation programs...
June 15, 2017: Development
https://www.readbyqxmd.com/read/28634261/autophagy-gene-fip200-in-neural-progenitors-non-cell-autonomously-controls-differentiation-by-regulating-microglia
#9
Chenran Wang, Syn Yeo, Michael A Haas, Jun-Lin Guan
Recent studies have shown important roles for autophagy genes in the regulation of different tissue stem cells, including neural stem/progenitor cells (NSCs). However, little is known about whether autophagy can regulate NSCs through cell-extrinsic mechanisms. Here, we show that deletion of an essential autophagy gene, FIP200, in NSCs increased expression of Ccl5 and Cxcl10 in a p53-independent manner, mediating increased infiltration of microglia into the subventricular zone of both FIP200hGFAP conditional knockout (cKO) and FIP200;p53hGFAP 2cKO mice...
June 20, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28634198/the-effect-of-sustained-virological-response-on-the-risk-of-extrahepatic-manifestations-of-hepatitis-c-virus-infection
#10
Parag Mahale, Eric A Engels, Ruosha Li, Harrys A Torres, Lu-Yu Hwang, Eric L Brown, Jennifer R Kramer
BACKGROUND AND AIM: Chronic HCV infection is associated with several extrahepatic manifestations (EHMs). Data on the effect of sustained virological response (SVR) on the risk of EHMs are limited. METHODS: We conducted a retrospective cohort study using data of patients from the US Veterans Affairs HCV Clinical Case Registry who had a positive HCV RNA test (10/1999-08/2009). Patients receiving interferon-based antiviral therapy (AVT) were identified. SVR was defined as negative HCV RNA at least 12 weeks after end of AVT...
June 20, 2017: Gut
https://www.readbyqxmd.com/read/28633934/the-impact-of-ordinate-scaling-on-the-visual-analysis-of-single-case-data
#11
Evan H Dart, Keith C Radley
Visual analysis is the primary method for detecting the presence of treatment effects in graphically displayed single-case data and it is often referred to as the "gold standard." Although researchers have developed standards for the application of visual analysis (e.g., Horner et al., 2005), over- and underestimation of effect size magnitude is not uncommon among analysts. Several characteristics have been identified as potential contributors to these errors; however, researchers have largely focused on characteristics of the data itself (e...
August 2017: Journal of School Psychology
https://www.readbyqxmd.com/read/28633918/traction-force-and-its-regulation-during-cytokinesis-in-dictyostelium-cells
#12
Md Golam Sarowar Jahan, Shigehiko Yumura
Cytokinesis is the final stage of cell division. Dictyostelium cells have multiple modes of cytokinesis, including cytokinesis A, B and C. Cytokinesis A is a conventional mode, which depends on myosin II in the contractile ring. Myosin II null cells divide depending on substratum-attachment (cytokinesis B) or in a multi-polar fashion independent of the cell cycle (cytokinesis C). We investigated the traction stress exerted by dividing cells in the three different modes using traction force microscopy. In all cases, the traction forces were directed inward from both poles...
June 12, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28633392/can-estimation-of-sodium-intake-be-improved-by-borrowing-information-from-other-variables
#13
Lawrence J Appel, David R Jacobs
Estimation of dietary sodium intake is problematic. The most accurate measure is average sodium excretion from multiple 24 hour urine collections, but such an approach is impractical. Using data from the Women's Health Initiative, Prentice and colleagues assessed the relationship of calibrated estimates of sodium and potassium excretion with cardiovascular outcomes. The calibrated estimates are a function of self-reported sodium/potassium ratio from a food frequency questionnaire, age, body mass index, race, supplement use, smoking status, education, income, and aspirin use...
June 14, 2017: American Journal of Epidemiology
https://www.readbyqxmd.com/read/28632910/withdrawn-hypnosis-for-children-undergoing-dental-treatment
#14
REVIEW
Sharifa Al-Harasi, Paul F Ashley, David R Moles, Susan Parekh, Val Walters
BACKGROUND: Managing children is a challenge that many dentists face. Many non-pharmacological techniques have been developed to manage anxiety and behavioural problems in children, such us: 'tell, show & do', positive reinforcement, modelling and hypnosis. The use of hypnosis is generally an overlooked area, hence the need for this review. OBJECTIVES: This systematic review attempted to answer the question: What is the effectiveness of hypnosis (with or without sedation) for behaviour management of children who are receiving dental care in order to allow successful completion of treatment?Null hypothesis: Hypnosis has no effect on the outcome of dental treatment of children...
June 20, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28631484/ocular-pharmacokinetics-of-therapeutic-antibodies-given-by-intravitreal-injection-estimation-of-retinal-permeabilities-using-a-3-compartment-semi-mechanistic-model
#15
Laurence A Hutton-Smith, Eamonn A Gaffney, Helen M Byrne, Philip K Maini, Kapil Gadkar, Norman Alan Mazer
Intravitreally (IVT) injected macromolecules for the treatment of age-related macular degeneration must permeate through the inner limiting membrane (ILM) into the retina and through the retinal pigment epithelium (RPE) to enter the choroid. A quantitative understanding of intraocular transport mechanisms, elimination pathways and the effect of molecular size, is currently incomplete. We present a semi-mechanistic, 3-compartment (retina, vitreous and aqueous) pharmacokinetic (PK) model, expressed using linear ordinary differential equations (ODEs), to describe the molecular concentrations following a single IVT injection...
June 20, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28630943/parasites-lacking-the-micronemal-protein-mic2-are-deficient-in-surface-attachment-and-host-cell-egress-but-remain-virulent-in-vivo
#16
Simon Gras, Allison Jackson, Stuart Woods, Gurman Pall, Jamie Whitelaw, Jacqueline M Leung, Gary E Ward, Craig W Roberts, Markus Meissner
Background: Micronemal proteins of the thrombospondin-related anonymous protein (TRAP) family are believed to play essential roles during gliding motility and host cell invasion by apicomplexan parasites, and currently represent major vaccine candidates against Plasmodium falciparum, the causative agent of malaria. However, recent evidence suggests that they play multiple and different roles than previously assumed. Here, we analyse a null mutant for MIC2, the TRAP homolog in Toxoplasma gondii. Methods: We performed a careful analysis of parasite motility in a 3D-environment, attachment under shear stress conditions, host cell invasion and in vivo virulence...
2017: Wellcome Open Research
https://www.readbyqxmd.com/read/28630322/tcte1-is-a-conserved-component-of-the-dynein-regulatory-complex-and-is-required-for-motility-and-metabolism-in-mouse-spermatozoa
#17
Julio M Castaneda, Rong Hua, Haruhiko Miyata, Asami Oji, Yueshuai Guo, Yiwei Cheng, Tao Zhou, Xuejiang Guo, Yiqiang Cui, Bin Shen, Zibin Wang, Zhibin Hu, Zuomin Zhou, Jiahao Sha, Renata Prunskaite-Hyyrylainen, Zhifeng Yu, Ramiro Ramirez-Solis, Masahito Ikawa, Martin M Matzuk, Mingxi Liu
Flagella and cilia are critical cellular organelles that provide a means for cells to sense and progress through their environment. The central component of flagella and cilia is the axoneme, which comprises the "9+2" microtubule arrangement, dynein arms, radial spokes, and the nexin-dynein regulatory complex (N-DRC). Failure to properly assemble components of the axoneme leads to defective flagella and in humans leads to a collection of diseases referred to as ciliopathies. Ciliopathies can manifest as severe syndromic diseases that affect lung and kidney function, central nervous system development, bone formation, visceral organ organization, and reproduction...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28630293/a-null-model-for-microbial-diversification
#18
Timothy J Straub, Olga Zhaxybayeva
Whether prokaryotes (Bacteria and Archaea) are naturally organized into phenotypically and genetically cohesive units comparable to animal or plant species remains contested, frustrating attempts to estimate how many such units there might be, or to identify the ecological roles they play. Analyses of gene sequences in various closely related prokaryotic groups reveal that sequence diversity is typically organized into distinct clusters, and processes such as periodic selection and extensive recombination are understood to be drivers of cluster formation ("speciation")...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28629147/proteomic-high-affinity-zn-2-trafficking-where-does-metallothionein-fit-in
#19
REVIEW
David H Petering, Afsana Mahim
The cellular constitution of Zn-proteins and Zn-dependent signaling depend on the capacity of Zn(2+) to find specific binding sites in the face of a plethora of other high affinity ligands. The most prominent of these is metallothionein (MT). It serves as a storage site for Zn(2+) under various conditions, and has chemical properties that support a dynamic role for MT in zinc trafficking. Consistent with these characteristics, changing the availability of zinc for cells and tissues causes rapid alteration of zinc bound to MT...
June 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28629018/the-bone-building-blues-self-hardening-copper-doped-calcium-phosphate-cement-and-its-in-vitro-assessment-against-mammalian-cells-and-bacteria
#20
Julietta V Rau, Victoria M Wu, Valerio Graziani, Inna V Fadeeva, Alexander S Fomin, Marco Fosca, Vuk Uskoković
A blue calcium phosphate cement with optimal self-hardening properties was synthesized by doping whitlockite (β-TCP) with copper ions. The mechanism and the kinetics of the cement solidification process were studied using energy dispersive X-ray diffraction and it was found out that hardening was accompanied by the phase transition from TCP to brushite. Reduced lattice parameters in all crystallographic directions resulting from the rather low (1:180) substitution rate of copper for calcium was consistent with the higher ionic radius of the latter...
October 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
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