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Lifespan development

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https://www.readbyqxmd.com/read/28646408/a-mechanism-based-pk-pd-model-for-hematological-toxicities-induced-by-antibody-drug-conjugates
#1
Sihem Ait-Oudhia, Weiyan Zhang, Donald E Mager
Antibody-drug conjugates (ADCs) are complex drug platforms composed of monoclonal antibodies (mAbs) conjugated to potent cytotoxic drugs (payloads) via chemical linkers, enabling selective payload delivery to neoplastic cells, resulting in improved efficacy and reduced toxicity. Brentuximab vedotin (Adcetris®, SGN-35) and adotrastuzumab emtansine (Kadcyla®, T-DM1) are the two FDA-approved and commercially available ADCs, and both drugs exhibit ADC-related thrombocytopenia and neutropenia. A pharmacokinetic/pharmacodynamic (PK/PD) model for ADCs was developed to identify the analyte from each ADC that is most associated with the observed hematopoietic toxicities and to determine the role of the apparent in vivo payload release rate on the severity of thrombocytopenia and neutropenia...
June 23, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28638324/stochastic-signatures-of-involuntary-head-micro-movements-can-be-used-to-classify-females-of-abide-into-different-subtypes-of-neurodevelopmental-disorders
#2
Elizabeth B Torres, Sejal Mistry, Carla Caballero, Caroline P Whyatt
Background: The approximate 5:1 male to female ratio in clinical detection of Autism Spectrum Disorder (ASD) prevents research from characterizing the female phenotype. Current open access repositories [such as those in the Autism Brain Imaging Data Exchange (ABIDE I-II)] contain large numbers of females to help begin providing a new characterization of females on the autistic spectrum. Here we introduce new methods to integrate data in a scale-free manner from continuous biophysical rhythms of the nervous systems and discrete (ordinal) observational scores...
2017: Frontiers in Integrative Neuroscience
https://www.readbyqxmd.com/read/28637735/development-of-the-tailored-rett-intervention-and-assessment-longitudinal-trial-database-and-the-rett-evaluation-of-symptoms-and-treatments-rest-questionnaire
#3
Paramala Santosh, Kate Lievesley, Federico Fiori, Jatinder Singh
INTRODUCTION: Rett syndrome (RTT) is a pervasive neurodevelopmental disorder that presents with deficits in brain functioning leading to language and learning regression, characteristic hand stereotypies and developmental delay. Different mutations in the gene implicated in RTT-methyl-CpG-binding protein 2 (MECP2) establishes RTT as a disorder with divergent symptomatology ranging from individuals with severe to milder phenotypes. A reliable and single multidimensional questionnaire is needed that can embrace all symptoms, and the relationships between them, and can map clinically meaningful data to symptomatology across the lifespan in patients with RTT...
June 21, 2017: BMJ Open
https://www.readbyqxmd.com/read/28636311/insights-into-integrated-lead-generation-and-target-identification-in-malaria-and-tuberculosis-drug-discovery
#4
John Okombo, Kelly Chibale
New, safe and effective drugs are urgently needed to treat and control malaria and tuberculosis, which affect millions of people annually. However, financial return on investment in the poor settings where these diseases are mostly prevalent is very minimal to support market-driven drug discovery and development. Moreover, the imminent loss of therapeutic lifespan of existing therapies due to evolution and spread of drug resistance further compounds the urgency to identify novel effective drugs. However, the advent of new public-private partnerships focused on tropical diseases and the recent release of large data sets by pharmaceutical companies on antimalarial and antituberculosis compounds derived from phenotypic whole cell high throughput screening have spurred renewed interest and opened new frontiers in malaria and tuberculosis drug discovery...
June 21, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28635509/induced-pluripotent-stem-cell-derived-dopaminergic-neurons-from-adult-common-marmoset-fibroblasts
#5
Scott C Vermilyea, Scott Guthrie, Michael Meyer, Kim Smuga-Otto, Katarina Braun, Sara Howden, James A Thomson, Su-Chun Zhang, Marina Emborg, Dr Thaddeus G Golos
The common marmoset monkey (Callithrix jacchus; Cj) is an advantageous nonhuman primate species for modeling age-related disorders, including Parkinson's disease, due to their shorter lifespan compared to macaques. Cj-derived induced pluripotent stem cells (Cj-iPSCs) from somatic cells are needed for in vitro disease modeling and testing regenerative medicine approaches. Here we report the development of a novel Cj-iPSC line derived from adult marmoset fibroblasts. The Cj-iPSCs showed potent pluripotency properties including development of mesodermal lineages in tumors after injection to immunocompromised mice, as well as ectoderm and endoderm lineages after in vitro differentiation regimens, demonstrating differentiated derivatives of all three embryonic layers...
June 21, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28631973/the-lifespan-self-esteem-scale-initial-validation-of-a-new-measure-of-global-self-esteem
#6
Michelle A Harris, M Brent Donnellan, Kali H Trzesniewski
This article introduces the Lifespan Self-Esteem Scale (LSE), a short measure of global self-esteem suitable for populations drawn from across the lifespan. Many existing measures of global self-esteem cannot be used across multiple developmental periods due to changes in item content, response formats, and other scale characteristics. This creates a need for a new lifespan scale so that changes in global self-esteem over time can be studied without confounding maturational changes with alterations in the measure...
February 21, 2017: Journal of Personality Assessment
https://www.readbyqxmd.com/read/28627281/mirroring-meaningful-actions-sensorimotor-learning-modulates-imitation-of-goal-directed-actions
#7
Caroline Catmur, Cecilia Heyes
Imitation is important in the development of social and technological skills throughout the lifespan. Experiments investigating the acquisition and modulation of imitation (and of its proposed neural substrate, the mirror neuron system) have produced evidence that the capacity for imitation depends on associative learning in which connections are formed between sensory and motor representations of actions. However, evidence that the development of imitation depends on associative learning has been found only for non-goal-directed actions...
June 19, 2017: Quarterly Journal of Experimental Psychology: QJEP
https://www.readbyqxmd.com/read/28626624/biocompatibility-and-in-vivo-operation-of-implantable-mesoporous-pvdf-based-nanogenerators
#8
Yanhao Yu, Haiyan Sun, Hakan Orbay, Feng Chen, Christopher G England, Weibo Cai, Xudong Wang
The rapid developments of implantable biomedical electronics give rise to the motivation of exploring efficient and durable self-powered charging system. In this paper, we report a mesoporous polyvinylidene fluoride (PVDF)-based implantable piezoelectric nanogenerator (NG) for in vivo biomechanical energy harvesting. The NG was built with a sponge-like mesoporous PVDF film and encapsulated by polydimethylsiloxane (PDMS). After embedding this NG into rodents, a Voc of ~200 mV was produced from the gentle movement of rodent muscle...
September 2016: Nano Energy
https://www.readbyqxmd.com/read/28624982/towards-ageing-well-use-it-or-lose-it-exercise-epigenetics-and-cognition
#9
Irene Maeve Rea
More and more people are living into the 90s or becoming centenarians. But, the gift of increased 'age span' seldom equates with an improved 'health-span'. Governments across the world are expressing concern about the epidemic of chronic disease, and have responded by initiating policies that make prevention, reduction and treatment of chronic disease, a public health priority. But understanding, how to age long and well, with the avoidance of chronic disease and later life complex disease morbidity is challenging...
June 17, 2017: Biogerontology
https://www.readbyqxmd.com/read/28621414/micrornas-in-drosophila-regulate-cell-fate-by-repressing-single-mrna-targets
#10
Noam Perry, Marina Volin, Hila Toledano
Regulation of gene expression governs all aspects of the lifespan of the organism, such as embryonic development, stem cell differentiation, reproduction and aging. Among the most important regulators of these extremely complex processes are microRNAs (miRNAs), small non-coding RNAs that repress gene expression by binding to primary sequences on the mRNA of their target. Theoretically, the mere existence of a miRNA recognition sequence on a given mRNA is sufficient to generate a functional response. Since these short sequences are abundant, one miRNA can potentially bind to multiple targets, thus generating endless possible biological outcomes...
2017: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/28619754/antitumor-effect-of-the-atypical-retinoid-st1926-in-acute-myeloid-leukemia-and-nanoparticle-formulation-prolongs-lifespan-and-reduces-tumor-burden-of-xenograft-mice
#11
Leeanna El-Houjeiri, Walid Saad, Berthe Hayar, Patrick Aouad, Nadim Tawil, Rana Abdel-Samad, Rita Hleihel, Maguy Hamie, Angelo Mancinelli, Claudio Pisano, Hiba El Hajj, Nadine Darwiche
Acute myeloid leukemia (AML) is one of the most frequent types of blood malignancies. It is a complex disorder of undifferentiated hematopoietic progenitor cells. The majority of patients generally respond to intensive therapy. Nevertheless, relapse is the major cause of death in AML, warranting the need for novel treatment strategies. Retinoids have demonstrated potent differentiation and growth regulatory effects in normal, transformed and hematopoietic progenitor cells. All-trans retinoic acid (ATRA) is the paradigm of treatment in acute promyelocytic leukemia, an AML subtype...
June 15, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28619165/the-use-of-animals-as-a-surveillance-tool-for-monitoring-environmental-health-hazards-human-health-hazards-and-bioterrorism
#12
REVIEW
Jacqueline Pei Shan Neo, Boon Huan Tan
This review discusses the utilization of wild or domestic animals as surveillance tools for monitoring naturally occurring environmental and human health hazards. Besides providing early warning to natural hazards, animals can also provide early warning to societal hazards like bioterrorism. Animals are ideal surveillance tools to humans because they share the same environment as humans and spend more time outdoors than humans, increasing their exposure risk. Furthermore, the biologically compressed lifespans of some animals may allow them to develop clinical signs more rapidly after exposure to specific pathogens...
May 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28611316/effects-of-resveratrol-curcumin-berberine-and-other-nutraceuticals-on-aging-cancer-development-cancer-stem-cells-and-micrornas
#13
James A McCubrey, Kvin Lertpiriyapong, Linda S Steelman, Steve L Abrams, Li V Yang, Ramiro M Murata, Pedro L Rosalen, Aurora Scalisi, Luca M Neri, Lucio Cocco, Stefano Ratti, Alberto M Martelli, Piotr Laidler, Joanna Dulińska-Litewka, Dariusz Rakus, Agnieszka Gizak, Paolo Lombardi, Ferdinando Nicoletti, Saverio Candido, Massimo Libra, Giuseppe Montalto, Melchiorre Cervello
Natural products or nutraceuticals have been shown to elicit anti-aging, anti-cancer and other health-enhancing effects. A key target of the effects of natural products may be the regulation of microRNA (miR) expression which results in cell death or prevents aging, diabetes, cardiovascular and other diseases. This review will focus on a few natural products, especially on resveratrol (RES), curcumin (CUR) and berberine (BBR). RES is obtained from the skins of grapes and other fruits and berries. RES may extend human lifespan by activating the sirtuins and SIRT1 molecules...
June 12, 2017: Aging
https://www.readbyqxmd.com/read/28608256/development-and-examination-of-a-functional-reactive-agility-test-for-older-adults
#14
Eric J Sobolewski, Brennan J Thompson, Eric C Conchola, Eric D Ryan
BACKGROUND: Reactive agility tests have become popular in sport for talent identification; however, the ability of these tests to evaluate physical function and falls risk in clinical populations warrants future study. AIM: To examine the reliability and construct validity of a novel functional reactive agility test (FRAT) across the lifespan. METHODS: Forty-three young (24 ± 2 years), 32 middle-aged (50 ± 2 years), and 19 old (66 ± 4 years) men performed a FRAT that included a rapid lateral movement (1...
June 12, 2017: Aging Clinical and Experimental Research
https://www.readbyqxmd.com/read/28606139/a-loss-of-pdxk-model-of-parkinson-disease-in-drosophila-can-be-suppressed-by-buffy
#15
P Githure M'Angale, Brian E Staveley
BACKGROUND: The identification of a DNA variant in pyridoxal kinase (Pdxk) associated with increased risk to Parkinson disease (PD) gene led us to study the inhibition of this gene in the Dopa decarboxylase (Ddc)-expressing neurons of the well-studied model organism Drosophila melanogaster. The multitude of biological functions attributable to the vitamers catalysed by this kinase reveal an overabundance of possible links to PD, that include dopamine synthesis, antioxidant activity and mitochondrial function...
June 12, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/28605645/novel-in-vivo-experimental-viability-assays-with-high-sensitivity-and-throughput-capacity-using-a-bdelloid-rotifer
#16
Zita Olah, Ashley I Bush, David Aleksza, Bence Galik, Eszter Ivitz, Lilla Macsai, Zoltan Janka, Zoltan Karman, Janos Kalman, Zsolt Datki
Rotifers have been used in biological research as well-characterized models of aging. Their multi-organ characters and their sensitivity for chemicals and environmental changes make them useful as in vivo toxicological and lifespan models. Our aim was to create a bdelloid rotifer model to use in high-throughput viability and non-invasive assays. In order to identify our species Philodina acuticornis odiosa (PA), 18S rDNA-based phylogenetic analysis was carried out and their species-specific morphological markers identified...
June 9, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28605149/increase-in-multiple-paternity-across-the-reproductive-lifespan-in-a-sperm-storing-hermaphroditic-freshwater-snail
#17
Anja Bürkli, Jukka Jokela
Polyandry is a common phenomenon and challenges the traditional view of stronger sexual selection in males than in females. In simultaneous hermaphrodites, the physical proximity of both sex functions was long thought to preclude the operation of sexual selection. Laboratory studies suggest that multiple mating and polyandry in hermaphrodites may actually be common, but data from natural populations are sparse. We therefore estimated the rate of multiple paternity and its seasonal variability in the annual, sperm-storing, simultaneously hermaphroditic freshwater snail Radix balthica for the entire duration of the reproductive lifespan...
June 12, 2017: Molecular Ecology
https://www.readbyqxmd.com/read/28594660/regulation-of-the-hematopoietic-stem-cell-lifecycle-by-the-endothelial-niche
#18
Pradeep Ramalingam, Michael G Poulos, Jason M Butler
PURPOSE OF REVIEW: Hematopoietic stem cells (HSCs) predominantly reside either in direct contact or in close proximity to the vascular endothelium throughout their lifespan. From the moment of HSC embryonic specification from hemogenic endothelium, endothelial cells (ECs) act as a critical cellular-hub that regulates a vast repertoire of biological processes crucial for HSC maintenance throughout its lifespan. In this review, we will discuss recent findings in endothelial niche-mediated regulation of HSC function during development, aging and regenerative conditions...
July 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28593990/loss-of-asxl2-leads-to-myeloid-malignancies-in-mice
#19
Jianping Li, Fuhong He, Peng Zhang, Shi Chen, Hui Shi, Yanling Sun, Ying Guo, Hui Yang, Na Man, Sarah Greenblatt, Zhaomin Li, Zhengyu Guo, Yuan Zhou, Lan Wang, Lluis Morey, Sion Williams, Xi Chen, Qun-Tian Wang, Stephen D Nimer, Peng Yu, Qian-Fei Wang, Mingjiang Xu, Feng-Chun Yang
ASXL2 is frequently mutated in acute myeloid leukaemia patients with t(8;21). However, the roles of ASXL2 in normal haematopoiesis and the pathogenesis of myeloid malignancies remain unknown. Here we show that deletion of Asxl2 in mice leads to the development of myelodysplastic syndrome (MDS)-like disease. Asxl2(-/-) mice have an increased bone marrow (BM) long-term haematopoietic stem cells (HSCs) and granulocyte-macrophage progenitors compared with wild-type controls. Recipients transplanted with Asxl2(-/-) and Asxl2(+/-) BM cells have shortened lifespan due to the development of MDS-like disease or myeloid leukaemia...
June 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28590932/tdp-43-hdac6-axis-promoted-tumor-progression-and-regulated-nutrient-deprivation-induced-autophagy-in-glioblastoma
#20
Tzu-Wei Lin, Ming-Teh Chen, Liang-Tin Lin, Pin-I Huang, Wen-Liang Lo, Yi-Ping Yang, Kai-Hsi Lu, Yi-Wei Chen, Shih-Hwa Chiou, Cheng-Wen Wu
Glioblastoma Multiforme (GBM) is a lethal primary brain tumor with poor survival lifespan and dismal outcome. Surgical resection of GBM is greatly limited due to the biological significance of brain, giving rise to tumor relapse in GBM patients. Transactive response DNA binding protein-43 (TDP-43) is a DNA/RNA-binding protein known for causing neurodegenerative diseases through post-translational modification; but little is known about its involvement in cancer development. In this study, we found that nutrient deprivation in GBM cell lines elevated TDP-43 expression by a mechanism of evasion from ubiquitin-dependent proteolytic pathway, and subsequently activated the autophagy process...
May 18, 2017: Oncotarget
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