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https://www.readbyqxmd.com/read/28445970/acid-ceramidase-is-a-novel-drug-target-for-pediatric-brain-tumors
#1
Ninh B Doan, Ha S Nguyen, Andrew Montoure, Mona M Al-Gizawiy, Wade M Mueller, Shekar Kurpad, Scott D Rand, Jennifer M Connelly, Christopher R Chitambar, Kathleen M Schmainda, Shama P Mirza
Pediatric brain tumors are the most common solid tumors in children and are also a leading culprit of cancer-related fatalities in children. Pediatric brain tumors remain hard to treat. In this study, we demonstrated that medulloblastoma, pediatric glioblastoma, and atypical teratoid rhabdoid tumors express significant levels of acid ceramidase, where levels are highest in the radioresistant tumors, suggesting that acid ceramidase may confer radioresistance. More importantly, we also showed that acid ceramidase inhibitors are highly effective at targeting these pediatric brain tumors with low IC50 values (4...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445940/suppression-of-allograft-rejection-by-cd8-cd122-pd-1-tregs-is-dictated-by-their-fas-ligand-initiated-killing-of-effector-t-cells-versus-fas-mediated-own-apoptosis
#2
Huazhen Liu, Yeshu Wang, Qiaohuang Zeng, Yu-Qun Zeng, Chun-Ling Liang, Feifei Qiu, Hong Nie, Zhenhua Dai
Mounting evidence has shown that naturally occurring CD8+CD122+ T cells are regulatory T cells (Tregs) that suppress both autoimmunity and alloimmunity. We have previously shown that CD8+CD122+PD-1+ Tregs not only suppress allograft rejection, but also are more potent in suppression than conventional CD4+CD25+ Tregs. However, the mechanisms underlying their suppression of alloimmunity are not well understood. In an adoptive T-cell transfer model of mice lacking lymphocytes, we found that suppression of skin allograft rejection by CD8+CD122+PD-1+ Tregs was mostly dependent on their expression of Fas ligand as either lacking Fas ligand or blocking it with antibodies largely abolished their suppression of allograft rejection mediated by transferred T cells...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445885/patterns-of-microglial-cell-activation-in-alzheimer-disease-and-frontotemporal-lobar-degeneration
#3
Ricardo Taipa, Paulo Brochado, Andrew Robinson, Inês Reis, Patrício Costa, David M Mann, Manuel Melo Pires, Nuno Sousa
AIMS: Microglia-driven neuroinflammation can play an important role in the pathophysiology of neurodegenerative disorders. In this study, we sought to characterize the distribution of microglial cell activation in 2 neurodegenerative dementias with distinct protein signatures, Alzheimer disease (AD) and frontotemporal lobar degeneration (FTLD) of the TDP subtype, and to determine if there was an anatomical correlation with the phenotypes most commonly associated with these conditions...
April 27, 2017: Neuro-degenerative Diseases
https://www.readbyqxmd.com/read/28445816/disinfection-byproduct-formation-in-drinking-water-sources-a-case-study-of-yuqiao-reservoir
#4
Hongyan Zhai, Xizhen He, Yan Zhang, Tingting Du, Adeyemi S Adeleye, Yao Li
This study investigated the potential formation of disinfection byproducts (DBPs) during chlorination and chloramination of 20 water samples collected from different points of Yuqiao reservoir in Tianjin, China. The concentrations of dissolved organic matter and ammonia decreased downstream the reservoir, while the specific UV absorbance (SUVA: the ratio of UV254 to dissolved organic carbon) increased [from 0.67 L/(mg*m) upstream to 3.58 L/(mg*m) downstream]. The raw water quality played an important role in the formation of DBPs...
April 15, 2017: Chemosphere
https://www.readbyqxmd.com/read/28445801/an-ahp-based-evaluation-method-for-teacher-training-workshop-on-information-and-communication-technology
#5
Rochelle Irene Lucas, Michael Angelo Promentilla, Aristotle Ubando, Raymond Girard Tan, Kathleen Aviso, Krista Danielle Yu
The emergence of information and communication technology (ICT) has created opportunities for enhancing the learning process at different educational levels. However, its potential benefits can only be fully realized if teachers are properly trained to utilize such tools. The rapid evolution of ICT also necessitates rigorous assessment of training programs by participants. Thus, this study proposes an evaluation framework based on the Analytic Hierarchy Process (AHP) to systematically evaluate such workshops designed for teachers...
April 19, 2017: Evaluation and Program Planning
https://www.readbyqxmd.com/read/28445782/the-immunohistochemical-distribution-of-the-gabaa-receptor-%C3%AE-1-%C3%AE-2-%C3%AE-3-%C3%AE-2-3-and-%C3%AE-2-subunits-in-the-human-thalamus
#6
H J Waldvogel, M Munkle, W van Roon-Mom, H Mohler, R L M Faull
The GABAA receptor is the most abundant inhibitory receptor in the human brain and is assembled from a variety of different subunit subtypes which determines their pharmacology and physiology. To determine which GABAA receptor subunit proteins are found in the human thalamus we investigated the distribution of five major GABAA receptor subunits α1, α2, α3, β2,3 and γ2 using immunohistochemical techniques. The α1-, β2,3- and γ2- subunits which combine to form a benzodiazepine sensitive GABAA receptor showed the most intense levels of staining and were the most common subunits found throughout the human thalamus especially in the ventral and posterior nuclear groups...
April 23, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/28445749/equilibrium-ensembles-for-insulin-folding-from-bias-exchange-metadynamics
#7
Richa Singh, Rohit Bansal, Anurag Singh Rathore, Gaurav Goel
Earliest events in the aggregation process, such as single molecule reconfiguration, are extremely important and the most difficult to characterize in experiments. To this end, we have used well-tempered bias exchange metadynamics simulations to determine the equilibrium ensembles of an insulin molecule under amyloidogenic conditions of low pH and high temperature. A bin-based clustering method that uses statistics accumulated in bias exchange metadynamics trajectories was employed to construct a detailed thermodynamic and kinetic model of insulin folding...
April 25, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28445748/directional-force-originating-from-atp-hydrolysis-drives-the-groel-conformational-change
#8
Jie Liu, Kannan Sankar, Yuan Wang, Kejue Jia, Robert L Jernigan
Protein functional mechanisms usually require conformational changes, and often there are known structures for the different conformational states. However, usually neither the origin of the driving force nor the underlying pathways for these conformational transitions is known. Exothermic chemical reactions may be an important source of forces that drive conformational changes. Here we investigate this type of force originating from ATP hydrolysis in the chaperonin GroEL, by applying forces originating from the chemical reaction...
April 25, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28445723/mosquitoes-transmit-unique-west-nile-virus-populations-during-each-feeding-episode
#9
Nathan D Grubaugh, Joseph R Fauver, Claudia Rückert, James Weger-Lucarelli, Selene Garcia-Luna, Reyes A Murrieta, Alex Gendernalik, Darci R Smith, Doug E Brackney, Gregory D Ebel
Arthropod-borne viruses (arboviruses), such as Zika virus, chikungunya virus, and West Nile virus (WNV), pose continuous threats to emerge and cause large epidemics. Often, these events are associated with novel virus variants optimized for local transmission that first arise as minorities within a host. Thus, the conditions that regulate the frequency of intrahost variants are important determinants of emergence. Here, we describe the dynamics of WNV genetic diversity during its transmission cycle. By temporally sampling saliva from individual mosquitoes, we demonstrate that virus populations expectorated by mosquitoes are highly diverse and unique to each feeding episode...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445697/influence-of-maturation-on-in-vivo-tissue-to-plasma-partition-coefficients-for-cis-and-trans-permethrin
#10
Manoj Amaraneni, Jing Pang, James V Bruckner, Srinivasa Muralidhara, Tanzir B Mortuza, Darren Gullick, Shirin Hooshfar, Catherine A White, Brian S Cummings
Permethrin, the most widely used household insecticide in the U.S., is marketed as a mixture of its cis (CIS) and trans (TRANS) isomers. The major objective of this investigation was to develop and utilize a reliable approach to determine in vivo partition coefficients (PCs) for CIS and TRANS in immature and adult Sprague-Dawley rats. Adult, postnatal day (PND) 21 and PND 15 rats were infused with environmentally relevant concentrations of CIS or TRANS via a s.c. osmotic pump for 48 or 72 h. The adult and PND 21 rats also received an oral loading dose...
April 23, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28445624/the-role-of-publicly-funded-family-planning-sites-in-health-insurance-enrollment
#11
Jennifer Yarger, Sara Daniel, M Antonia Biggs, Jan Malvin, Claire D Brindis
CONTEXT: Publicly funded family planning providers are well positioned to help uninsured individuals learn about health insurance coverage options and effectively navigate the enrollment process. Understanding how these providers are engaged in enrollment assistance and the challenges they face in providing assistance is important for maximizing their role in health insurance outreach and enrollment. METHODS: In 2014, some 684 sites participating in California's family planning program were surveyed about their involvement in helping clients enroll in health insurance...
April 26, 2017: Perspectives on Sexual and Reproductive Health
https://www.readbyqxmd.com/read/28445601/status-epilepticus-in-dogs-and-cats-part-2-treatment-monitoring-and-prognosis
#12
Susan Blades Golubovic, John H Rossmeisl
OBJECTIVE: To discuss current anticonvulsant drug options and advances in treatment of status epilepticus (SE) and to review the prognosis associated with SE. TREATMENT: When treating a patient with SE, the main goals are to halt seizure activity, prevent further seizures, identify the cause of the seizures, and manage any complications. The veterinary literature indicates that benzodiazepines are the most common class of drugs used for the initial treatment of SE...
April 26, 2017: Journal of Veterinary Emergency and Critical Care
https://www.readbyqxmd.com/read/28445588/the-relative-importance-of-pollinator-abundance-and-species-richness-for-the-temporal-variance-of-pollination-services
#13
Mark A Genung, Jeremy Fox, Neal M Williams, Claire Kremen, John Ascher, Jason Gibbs, Rachael Winfree
The relationship between biodiversity and the stability of ecosystem function is a fundamental question in community ecology, and hundreds of experiments have shown a positive relationship between species richness and the stability of ecosystem function. However, these experiments have rarely accounted for common ecological patterns, most notably skewed species abundance distributions and non-random extinction risks, making it difficult to know whether experimental results can be scaled up to larger, less manipulated systems...
April 26, 2017: Ecology
https://www.readbyqxmd.com/read/28445561/allegations-of-failure-to-obtain-informed-consent-in-spinal-surgery-medical-malpractice-claims
#14
Jennifer Grauberger, Panagiotis Kerezoudis, Asad J Choudhry, Mohammed Ali Alvi, Ahmad Nassr, Bradford Currier, Mohamad Bydon
Importance: Predictive factors associated with increased risk of medical malpractice litigation have been identified, including severity of injury, physician sex, and error in diagnosis. However, there is a paucity of literature investigating informed consent in spinal surgery malpractice. Objective: To investigate the failure to obtain informed consent as an allegation in medical malpractice claims for patients undergoing a spinal procedure. Design, Setting, and Participants: In this retrospective cohort study, a national medicolegal database was searched for malpractice claim cases related to spinal surgery for all years available (ie, January 1, 1980, through December 31, 2015)...
April 26, 2017: JAMA Surgery
https://www.readbyqxmd.com/read/28445558/clinical-characteristics-of-connective-tissue-nevi-in-tuberous-sclerosis-complex-with-special-emphasis-on-shagreen-patches
#15
Michelle A Bongiorno, Neera Nathan, Oyetewa Oyerinde, Ji-An Wang, Chyi-Chia Richard Lee, G Thomas Brown, Joel Moss, Thomas N Darling
Importance: Patients with tuberous sclerosis complex (TSC) frequently develop collagenous connective tissue nevi. The prototypical lesion is a large shagreen patch located on the lower back, but some patients only manifest small collagenomas or have lesions elsewhere on the body. The ability to recognize these variable presentations can be important for the diagnosis of TSC. Objective: To describe the clinical characteristics of connective tissue nevi on the trunk and extremities of patients with tuberous sclerosis complex...
April 26, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/28445522/revealing-phenotype-associated-functional-differences-by-genome-wide-scan-of-ancient-haplotype-blocks
#16
Ritsuko Onuki, Rui Yamaguchi, Tetsuo Shibuya, Minoru Kanehisa, Susumu Goto
Genome-wide scans for positive selection have become important for genomic medicine, and many studies aim to find genomic regions affected by positive selection that are associated with risk allele variations among populations. Most such studies are designed to detect recent positive selection. However, we hypothesize that ancient positive selection is also important for adaptation to pathogens, and has affected current immune-mediated common diseases. Based on this hypothesis, we developed a novel linkage disequilibrium-based pipeline, which aims to detect regions associated with ancient positive selection across populations from single nucleotide polymorphism (SNP) data...
2017: PloS One
https://www.readbyqxmd.com/read/28445514/the-complexity-underlying-invasiveness-precludes-the-identification-of-invasive-traits-a-comparative-study-of-invasive-and-non-invasive-heterocarpic-atriplex-congeners
#17
Jana Doudová, Jan Douda, Bohumil Mandák
Heterocarpy enables species to effectively spread under unfavourable conditions by producing two or more types of fruit differing in ecological characteristics. Although it is frequent in annuals occupying disturbed habitats that are vulnerable to invasion, there is still a lack of congeneric studies addressing the importance of heterocarpy for species invasion success. We compared two pairs of heterocarpic Atriplex species, each of them comprising one invasive and one non-invasive non-native congener. In two common garden experiments, we (i) simulated the influence of different levels of nutrients and population density on plants grown from different types of fruits and examined several traits that are generally positively associated with invasion success, and (ii) grew plants in a replacement series experiment to evaluate resource partitioning between them and to compare their competitive ability...
2017: PloS One
https://www.readbyqxmd.com/read/28445464/burgess-shale-fossils-illustrate-the-origin-of-the-mandibulate-body-plan
#18
Cédric Aria, Jean-Bernard Caron
Retracing the evolutionary history of arthropods has been one of the greatest challenges in biology. During the past decade, phylogenetic analyses of morphological and molecular data have coalesced towards the conclusion that Mandibulata, the most diverse and abundant group of animals, is a distinct clade from Chelicerata, in that its members possess post-oral head appendages specialized for food processing, notably the mandible. The origin of the mandibulate body plan, however, which encompasses myriapods, crustaceans and hexapods, has remained poorly documented...
April 26, 2017: Nature
https://www.readbyqxmd.com/read/28445439/her2-in-breast-cancer-stemness-a-negative-feedback-loop-towards-trastuzumab-resistance
#19
REVIEW
Babak Nami, Zhixiang Wang
HER2 receptor tyrosine kinase that is overexpressed in approximately 20% of all breast cancers (BCs) is a poor prognosis factor and a precious target for BC therapy. Trastuzumab is approved by FDA to specifically target HER2 for treating HER2+ BC. However, about 60% of patients with HER2+ breast tumor develop de novo resistance to trastuzumab, partially due to the loss of expression of HER2 extracellular domain on their tumor cells. This is due to shedding/cleavage of HER2 by metalloproteinases (ADAMs and MMPs)...
April 26, 2017: Cancers
https://www.readbyqxmd.com/read/28445360/facial-danger-zones-techniques-to-maximize-safety-during-soft-tissue-filler-injections
#20
Jack F Scheuer, David A Sieber, Ronnie A Pezeshk, Andrew A Gassman, Carey F Campbell, Rod J Rohrich
Given the short recovery and immediate results, facial fillers have become a popular alternative to surgical rejuvenation of the face. Reported complications arising from facial filler injections include erythema, tissue loss, blindness, stroke, and even death. In this article, the authors describe their anatomically based techniques to minimize risk and maximize safety when injecting in the facial danger zones, including the glabella/brow, temporal region, perioral region, nasolabial fold, nose, and infraorbital region...
May 2017: Plastic and Reconstructive Surgery
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