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https://www.readbyqxmd.com/read/28651365/cathepsin-k-inhibitors-for-osteoporosis-biology-potential-clinical-utility-and-lessons-learned
#1
Matthew T Drake, Bart L Clarke, Merry Jo Oursler, Sundeep Khosla
Cathepsin K is a cysteine protease member of the cathepsin lysosomal protease family. While cathepsin K is highly expressed in osteoclasts, lower levels of cathepsin K are also found in a variety of other tissues. Secretion of cathepsin K from the osteoclast into the sealed osteoclast-bone cell interface results in efficient degradation of type I collagen. The absence of cathepsin K activity in humans results in pycnodysostosis, characterized by increased bone mineral density and fractures. Pharmacological cathepsin K inhibition leads to continuous increases in BMD for up to five years of treatment and improves bone strength at the spine and hip...
June 23, 2017: Endocrine Reviews
https://www.readbyqxmd.com/read/28651357/using-viral-gene-sequences-to-compare-and-explain-the-heterogeneous-spatial-dynamics-of-virus-epidemics
#2
Simon Dellicour, Rebecca Rose, Nuno Rodrigues Faria, Luiz Fernando Pereira Vieira, Hervé Bourhy, Marius Gilbert, Philippe Lemey, Oliver G Pybus
Rabies is an important zoonotic disease distributed worldwide. A key question in rabies epidemiology is the identification of factors that impact virus dispersion. Here we apply new analytical methods, based on phylogeographic reconstructions of viral lineage movement, to undertake a comparative evolutionary-epidemiological study of the spatial dynamics of rabies virus (RABV) epidemics in different hosts and habitats. We have compiled RABV data sets from skunk, raccoon, bat and domestic dog populations in order to investigate the viral diffusivity of different RABV epidemics, and detect and compare those environmental factors that impact the velocity of viral spread in continuous spatial landscapes...
June 23, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28651344/uterine-responses-to-early-pre-attachment-embryos-in-the-domestic-dog-and-comparisons-with-other-domestic-animal-species
#3
Felix R Graubner, Aykut Gram, Ewa Kautz, Stefan Bauersachs, Selim Aslan, Ali R Agaoglu, Alois Boos, Mariusz P Kowalewski
In the dog there is no luteolysis in the absence of pregnancy. Thus, this species lacks any anti-luteolytic endocrine signal as found in other species that modulate uterine function during the critical period of pregnancy establishment. Nevertheless, in the dog an embryo-maternal communication must occur in order to prevent rejection of embryos. Based on this hypothesis, we performed microarray analysis of canine uterine samples collected during pre-attachment phase (days 10-12) and in corresponding non-pregnant controls, in order to elucidate the embryo attachment signal...
June 23, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28651316/a-permeation-controlled-formaldehyde-reference-source-for-application-in-environmental-test-chambers
#4
Tunga Salthammer, Ruth Giesen, Tobias Schripp
In a wide range of indoor air pollutants, formaldehyde is one of the most-used and best-known substances. In order to protect human health, many countries have established threshold values for the release of formaldehyde from miscellaneous products and revise them constantly. Compliance with these regulations is usually assessed by emission test chamber measurements or derived methods. To control and improve the mechanisms of an emission test chamber, a reliable reference source with sample mimicking emission properties is required but not available so far...
June 15, 2017: Chemosphere
https://www.readbyqxmd.com/read/28651240/indirect-spectrophotometric-determination-of-sulfadiazine-based-on-localized-surface-plasmon-resonance-peak-of-silver-nanoparticles-after-cloud-point-extraction
#5
Elahe Kazemi, Shayessteh Dadfarnia, Ali Mohammad Haji Shabani, Mohammad Reza Fattahi, Javad Khodaveisi
A novel, efficient, easy to use, environmentally friendly and cost-effective methodology is developed for the indirect spectrophotometric determination of sulfadiazine in different samples. The method is based on the micelle-mediated extraction of silver sulfadiazine and converting the silver content of the resultant surfactant-rich phase to the silver nanoparticles via generation of [Ag(NH3)2](+) followed by its chemical reduction using ascorbic acid. The changes in the amplitude of localized surface plasmon resonance peak of silver nanoparticles as a function of sulfadiazine concentration in the sample solution was monitored using fiber optic linear array spectrophotometry at 457nm...
June 17, 2017: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/28651222/assessing-habitat-quality-in-relation-to-the-spatial-distribution-of-protected-areas-in-italy
#6
Lorenzo Sallustio, Andrea De Toni, Andrea Strollo, Mirko Di Febbraro, Elena Gissi, Laura Casella, Davide Geneletti, Michele Munafò, Matteo Vizzarri, Marco Marchetti
The conservation of species and habitats is increasingly threatened by anthropogenic impacts, particularly land use change, from local to global scales. Although many efforts have been carried out so far to halt or at least reduce the biodiversity loss (e.g., the establishment of protected areas' networks), there are still both knowledge and policy gaps slowing the conservation of species and habitats in complex environments, such as the Mediterranean region. In particular, the human-driven impacts and threats on biodiversity need more careful analysis...
June 23, 2017: Journal of Environmental Management
https://www.readbyqxmd.com/read/28651166/air-quality-inside-subway-metro-indoor-environment-worldwide-a-review
#7
REVIEW
Bin Xu, Jinliang Hao
The air quality in the subway metro indoor microenvironment has been of particular public concern. With specific reference to the growing demand of green transportation and sustainable development, subway metro systems have been rapidly developed worldwide in last decades. The number of metro commuters has continuously increased over recent years in metropolitan cities. In some cities, metro system has become the primary public transportation mode. Although commuters typically spend only 30-40min in metros, the air pollutants emitted from various interior components of metro system as well as air pollutants carried by ventilation supply air are significant sources of harmful air pollutants that could lead to unhealthy human exposure...
June 23, 2017: Environment International
https://www.readbyqxmd.com/read/28651114/isolation-and-functional-interrogation-of-adult-human-prostate-epithelial-stem-cells-at-single-cell-resolution
#8
Wen-Yang Hu, Dan-Ping Hu, Lishi Xie, Ye Li, Shyama Majumdar, Larisa Nonn, Hong Hu, Toshi Shioda, Gail S Prins
Using primary cultures of normal human prostate epithelial cells, we developed a novel prostasphere-based, label-retention assay that permits identification and isolation of stem cells at a single cell level. Their bona fide stem cell nature was corroborated using in vitro and in vivo regenerative assays and documentation of symmetric/asymmetric division. Robust WNT10B and KRT13 levels without E-cadherin or KRT14 staining distinguished individual stem cells from daughter progenitors in spheroids. Following FACS to isolate label-retaining stem cells from label-free progenitors, RNA-seq identified unique gene signatures for the separate populations which may serve as useful biomarkers...
June 16, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28651088/genetic-and-epigenetic-alterations-in-normal-and-sensitive-copd-diseased-human-bronchial-epithelial-cells-repeatedly-exposed-to-air-pollution-derived-pm2-5
#9
B Leclercq, A Platel, S Antherieu, L Y Alleman, E M Hardy, E Perdrix, N Grova, V Riffault, B M Appenzeller, M Happillon, F Nesslany, P Coddeville, J-M Lo-Guidice, G Garçon
Even though clinical, epidemiological and toxicological studies have progressively provided a better knowledge of the underlying mechanisms by which air pollution-derived particulate matter (PM) exerts its harmful health effects, further in vitro studies on relevant cell systems are still needed. Hence, aiming of getting closer to the human in vivo conditions, primary human bronchial epithelial cells derived from normal subjects (NHBE) or sensitive chronic obstructive pulmonary disease (COPD)-diseased patients (DHBE) were differentiated at the air-liquid interface...
June 23, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28651066/thalassemia-major-transfusion-and-chelation-or-transplantation
#10
REVIEW
Said Yousuf Mohamed
Thalassemia is the most common monogenic hematologic disease that affects millions in the world and kills thousands of patients every year. Without transfusion or transplantation, patients with thalassemia major are expected to die within months of diagnosis. However, long-term transfusion and chelation therapy is highly challenging for many developing countries where the disease is prevalent, representing a major and unsustainable health burden. Stem cell transplantation is the only cure for thalassemia. It has witnessed major developments that have made it less toxic, more successful, and feasible for a larger number of patients with diverse comorbidities and from a wider range of donors...
June 20, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28651012/the-economic-burden-of-human-papillomavirus-related-precancers-and-cancers-in-sweden
#11
Ellinor Östensson, Maria Silfverschiöld, Lennart Greiff, Christine Asciutto, Johan Wennerberg, Marie-Louise Lydryp, Ulf Håkansson, Pär Sparén, Christer Borgfeldt
BACKGROUND: High-risk (HR) human papillomavirus (HPV) infection is an established cause of malignant disease. We used a societal perspective to estimate the cost of HR HPV-related cervical, vulvar, vaginal, anal, and penile precancer and cancer, and oropharyngeal cancer in Sweden in 2006, 1 year before HPV vaccination became available in the country. MATERIALS AND METHODS: This prevalence-based cost-of-illness study used diagnosis-specific data from national registries to determine the number of HR HPV-related precancers and cancers...
2017: PloS One
https://www.readbyqxmd.com/read/28651004/a-human-endogenous-retrovirus-derived-gene-that-can-contribute-to-oncogenesis-by-activating-the-erk-pathway-and-inducing-migration-and-invasion
#12
Cécile Lemaître, Jhen Tsang, Caroline Bireau, Thierry Heidmann, Marie Dewannieux
Endogenous retroviruses are cellular genes of retroviral origin captured by their host during the course of evolution and represent around 8% of the human genome. Although most are defective and transcriptionally silenced, some are still able to generate retroviral-like particles and proteins. Among these, the HERV-K(HML2) family is remarkable since its members have amplified relatively recently and many of them still have full length coding genes. Furthermore, they are induced in cancers, especially in melanoma, breast cancer and germ cell tumours, where viral particles, as well as the envelope protein (Env), can be detected...
June 26, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28650999/an-ancestral-haplotype-of-the-human-period2-gene-associates-with-reduced-sensitivity-to-light-induced-melatonin-suppression
#13
Tokiho Akiyama, Takafumi Katsumura, Shigeki Nakagome, Sang-Il Lee, Keiichiro Joh, Hidenobu Soejima, Kazuma Fujimoto, Ryosuke Kimura, Hajime Ishida, Tsunehiko Hanihara, Akira Yasukouchi, Yoko Satta, Shigekazu Higuchi, Hiroki Oota
Humans show various responses to the environmental stimulus in individual levels as "physiological variations." However, it has been unclear if these are caused by genetic variations. In this study, we examined the association between the physiological variation of response to light-stimulus and genetic polymorphisms. We collected physiological data from 43 subjects, including light-induced melatonin suppression, and performed haplotype analyses on the clock genes, PER2 and PER3, exhibiting geographical differentiation of allele frequencies...
2017: PloS One
https://www.readbyqxmd.com/read/28650985/chronic-trichuris-muris-infection-causes-neoplastic-change-in-the-intestine-and-exacerbates-tumour-formation-in-apc-min-mice
#14
Kelly S Hayes, Laura J Cliffe, Alison J Bancroft, Simon P Forman, Seona Thompson, Cath Booth, Richard K Grencis
Incidences of infection-related cancers are on the rise in developing countries where the prevalence of intestinal nematode worm infections are also high. Trichuris muris (T. muris) is a murine gut-dwelling nematode that is the direct model for human T. trichiura, one of the major soil-transmitted helminth infections of humans. In order to assess whether chronic infection with T. muris does indeed influence the development of cancer hallmarks, both wild type mice and colon cancer model (APC min/+) mice were infected with this parasite...
June 26, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28650973/interferon-signaling-in-peromyscus-leucopus-confers-a-potent-and-specific-restriction-to-vector-borne-flaviviruses
#15
Adaeze O Izuogu, Kristin L McNally, Stephen E Harris, Brian H Youseff, John B Presloid, Christopher Burlak, Jason Munshi-South, Sonja M Best, R Travis Taylor
Tick-borne flaviviruses (TBFVs), including Powassan virus and tick-borne encephalitis virus cause encephalitis or hemorrhagic fevers in humans with case-fatality rates ranging from 1-30%. Despite severe disease in humans, TBFV infection of natural rodent hosts has little noticeable effect. Currently, the basis for resistance to disease is not known. We hypothesize that the coevolution of flaviviruses with their respective hosts has shaped the evolution of potent antiviral factors that suppress virus replication and protect the host from lethal infection...
2017: PloS One
https://www.readbyqxmd.com/read/28650933/cyp2e1-gene-polymorphisms-related-to-the-formation-of-coronary-artery-lesions-in-kawasaki-disease
#16
Ling-Sai Chang, Yu-Wen Hsu, Chien-Chang Lu, Mao-Hung Lo, Kai-Sheng Hsieh, Sung-Chou Li, Wei-Chiao Chang, Ho-Chang Kuo
BACKGROUND: Kawasaki disease (KD) is an acute febrile systemic vasculitis that disturbs coronary arteries. Patients' risks of adverse cardiovascular events and subclinical atherosclerosis have been found to significantly increase with polymorphisms of the human cytochrome P450. This current study aims to research the possible relationship between Cytochrome P450, Family 2, Subfamily E, and Polypeptide 1 (CYP2E1) polymorphisms with KD. METHODS: We selected six tag single-nucleotide polymorphisms (tSNPs) of the CYP2E1 gene for TaqMan allelic discrimination assay in 340 KD patients and performed analysis on the clinical phenotypes and coronary artery lesions (CAL)...
June 23, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28650648/indian-ocean-dipole-and-cryptosporidiosis-in-australia-short-term-and-nonlinear-associations
#17
Aparna Lal, Masahiro Hashizume, Simon Hales
The Indian Ocean Dipole (IOD) is a global climate phenomenon that influences the spread of human infectious diseases through climate extremes including droughts and floods. The Dipole Mode Index (DMI), which measures the strength of the IOD, is one of the main indicators of rainfall variability across Australia. Using an ecological, time-series approach we examined the short-term and nonlinear relationship between the DMI and weekly cryptosporidiosis reported from 2001 to 2012 across the temperate, subtropical, and tropical climate zones in Australia, controlling for season, long-term trends, and cryptosporidiosis counts from the past week...
June 26, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28650473/testes-specific-protease-50-promotes-cell-proliferation-via-inhibiting-activin-signaling
#18
Z-B Song, P Wu, J-S Ni, T Liu, C Fan, Y-L Bao, Y Wu, L-G Sun, C-L Yu, Y-X Huang, Y-X Li
Testes-specific protease 50 (TSP50), a novelly identified oncogene, has the capacity to induce cell proliferation, cell invasion and tumor growth. Further studies indicated that CAGA-luc (an activin-responsive reporter construct) reporter activity could be significantly suppressed by TSP50 overexpression, implying that the activin signaling may participate in TSP50-mediated cell proliferation. Here, we reported that TSP50 had an inhibitory effect on activin signaling. Mechanistic studies revealed that TSP50 could interact with ActRIIA, inhibit activin typeIreceptor (ActRIB) phosphorylation, repress Smad2/3 nuclear accumulation and finally promote cell proliferation by reducing the expression of activin signal target gene p27...
June 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28650469/a-compartmentalized-phosphoinositide-signaling-axis-at-cilia-is-regulated-by-inpp5e-to-maintain-cilia-and-promote-sonic-hedgehog-medulloblastoma
#19
S E Conduit, V Ramaswamy, M Remke, D N Watkins, B J Wainwright, M D Taylor, C A Mitchell, J M Dyson
Sonic Hedgehog (SHH) signaling at primary cilia drives the proliferation and progression of a subset of medulloblastomas, the most common malignant paediatric brain tumor. Severe side effects associated with conventional treatments and resistance to targeted therapies has led to the need for new strategies. SHH signaling is dependent on primary cilia for signal transduction suggesting the potential for cilia destabilizing mechanisms as a therapeutic target. INPP5E is an inositol polyphosphate 5-phosphatase that hydrolyses PtdIns(4,5)P2 and more potently, the phosphoinositide (PI) 3-kinase product PtdIns(3,4,5)P3...
June 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28650457/fibroblast-growth-factor-19-regulates-skeletal-muscle-mass-and-ameliorates-muscle-wasting-in-mice
#20
Bérengère Benoit, Emmanuelle Meugnier, Martina Castelli, Stéphanie Chanon, Aurélie Vieille-Marchiset, Christine Durand, Nadia Bendridi, Sandra Pesenti, Pierre-Axel Monternier, Anne-Cécile Durieux, Damien Freyssenet, Jennifer Rieusset, Etienne Lefai, Hubert Vidal, Jérôme Ruzzin
The endocrine-derived hormone fibroblast growth factor (FGF) 19 has recently emerged as a potential target for treating metabolic disease. Given that skeletal muscle is a key metabolic organ, we explored the role of FGF19 in that tissue. Here we report a novel function of FGF19 in regulating skeletal muscle mass through enlargement of muscle fiber size, and in protecting muscle from atrophy. Treatment with FGF19 causes skeletal muscle hypertrophy in mice, while physiological and pharmacological doses of FGF19 substantially increase the size of human myotubes in vitro...
June 26, 2017: Nature Medicine
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