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https://www.readbyqxmd.com/read/28738360/targeting-developmental-pathways-the-achilles-heel-of-cancer
#1
Wolfram C M Dempke, Klaus Fenchel, Peter Uciechowski, Timothy Chevassut
Developmental pathways (e.g., Notch, Hippo, Hedgehog, Wnt, and TGF-β/BMP/FGF) are networks of genes that act co-ordinately to establish the body plan, and disruptions of genes in one pathway can have effects in related pathways and may result in serious dysmorphogenesis or cancer. Interestingly, all developmental pathways are highly conserved cell signalling systems present in almost all multicellular organisms. In addition, they have a crucial role in cell proliferation, apoptosis, differentiation, and finally in organ development...
July 22, 2017: Oncology
https://www.readbyqxmd.com/read/28738127/early-onset-alzheimer-disease-and-candidate-risk-genes-involved-in-endolysosomal-transport
#2
Brian W Kunkle, Badri N Vardarajan, Adam C Naj, Patrice L Whitehead, Sophie Rolati, Susan Slifer, Regina M Carney, Michael L Cuccaro, Jeffery M Vance, John R Gilbert, Li-San Wang, Lindsay A Farrer, Christiane Reitz, Jonathan L Haines, Gary W Beecham, Eden R Martin, Gerard D Schellenberg, Richard P Mayeux, Margaret A Pericak-Vance
Importance: Mutations in APP, PSEN1, and PSEN2 lead to early-onset Alzheimer disease (EOAD) but account for only approximately 11% of EOAD overall, leaving most of the genetic risk for the most severe form of Alzheimer disease unexplained. This extreme phenotype likely harbors highly penetrant risk variants, making it primed for discovery of novel risk genes and pathways for AD. Objective: To search for rare variants contributing to the risk for EOAD. Design, Setting, and Participants: In this case-control study, whole-exome sequencing (WES) was performed in 51 non-Hispanic white (NHW) patients with EOAD (age at onset <65 years) and 19 Caribbean Hispanic families previously screened as negative for established APP, PSEN1, and PSEN2 causal variants...
July 24, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28738084/the-dkk3-gene-encodes-a-vital-intracellular-regulator-of-cell-proliferation
#3
Jack L Leonard, Deborah M Leonard, Scot A Wolfe, Jilin Liu, Jaime Rivera, Michelle Yang, Ryan T Leonard, Jacob P S Johnson, Prashant Kumar, Kate L Liebmann, Amanda A Tutto, Zhongming Mou, Karl J Simin
Members of the Dickkopf (Dkk) family of Wnt antagonists interrupt Wnt-induced receptor assembly and participate in axial patterning and cell fate determination. One family member, DKK3, does not block Wnt receptor activation. Loss of Dkk3 expression in cancer is associated with hyperproliferation and dysregulated ß-catenin signaling, and ectopic expression of Dkk3 halts cancer growth. The molecular events mediating the DKK3-dependent arrest of ß-catenin-driven cell proliferation in cancer cells are unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28737788/a-multiscale-agent-based-framework-integrated-with-a-constraint-based-metabolic-network-model-of-cancer-for-simulating-avascular-tumor-growth
#4
Mehrdad Ghadiri, Mahshid Heidari, Sayed-Amir Marashi, Seyed Hasan Mousavi
In recent years, many efforts have been made in the field of computational modeling of cancerous tumors, in order to obtain a better understanding and predictions of their growth patterns. Furthermore, constraint-based modeling of metabolic networks has become increasingly popular, which is appropriate for the systems-level reconstruction of cell physiology. The goal of the current study is to integrate a multiscale agent-based modeling framework with a constraint-based metabolic network model of cancer cells in order to simulate the three dimensional early growth of avascular tumors...
July 24, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28737761/glutamate-receptor-like-channels-are-essential-for-chemotaxis-and-reproduction-in-mosses
#5
Carlos Ortiz-Ramírez, Erwan Michard, Alexander A Simon, Daniel S C Damineli, Marcela Hernández-Coronado, Jörg D Becker, José A Feijó
Glutamate receptors are well characterized channels that mediate cell-to-cell communication during neurotransmission in animals. Nevertheless, information regarding their functional role in organisms without nervous systems is still limited. In plants, Glutamate Receptor-like (GLR) genes have been implicated in defence against pathogens, reproduction, control of stomata aperture and light signal transduction(1-5). However, the numerous GLR genes present in angiosperm genomes (20 to 70)(6) has prevented the observation of strong phenotypes in loss-of-function mutants...
July 24, 2017: Nature
https://www.readbyqxmd.com/read/28737247/a-single-base-deletion-in-the-slc45a2-gene-in-a-bullmastiff-with-oculocutaneous-albinism
#6
M Caduff, A Bauer, V Jagannathan, T Leeb
Oculocutaneous albinism type 4 (OCA4) in humans and similar phenotypes in many animal species are caused by variants in the SLC45A2 gene, encoding a putative sugar transporter. In dog, two independent SLC45A2 variants are known that cause oculocutaneous albinism in Doberman Pinschers and several small dog breeds respectively. For the present study, we investigated a Bullmastiff with oculocutaneous albinism. The affected dog was highly inbred and resulted from the mating of a sire to its own grandmother. We obtained whole genome sequence data from the affected dog and searched specifically for variants in candidate genes known to cause albinism...
July 24, 2017: Animal Genetics
https://www.readbyqxmd.com/read/28736820/disease-causing-variants-in-the-atl1-gene-are-a-rare-cause-of-hereditary-spastic-paraplegia-among-czech-patients
#7
Anna Uhrová Mészárosová, Dagmar Grečmalová, Michaela Brázdilová, Nina Dvořáčková, Zdeněk Kalina, Marie Čermáková, Dagmar Vávrová, Irena Smetanová, David Staněk, Pavel Seeman
Variants in the ATL1 gene have been repeatedly described as the second most frequent cause of hereditary spastic paraplegia (HSP), a motor neuron disease manifested by progressive lower limb spasticity and weakness. Variants in ATL1 have been described mainly in patients with early onset HSP. We performed Sanger sequencing of all coding exons and adjacent intron regions of the ALT1 gene in 111 Czech patients with pure form of HSP and additional Multiplex-Ligation Probe Analysis (MLPA) testing targeting the ATL1 gene in 56 of them...
July 23, 2017: Annals of Human Genetics
https://www.readbyqxmd.com/read/28736767/activation-of-mosquito-complement-antiplasmodial-response-requires-cellular-immunity
#8
Julio César Castillo, Ana Beatriz Barletta Ferreira, Nathanie Trisnadi, Carolina Barillas-Mury
The mosquito complement-like system is a major defense mechanism that limits Plasmodium infection. Ookinete midgut invasion results in irreversible damage to invaded cells and triggers epithelial nitration and complement activation. Several lines of evidence suggest that hemocytes participate in early antiplasmodial responses that target ookinetes, but their role remains unclear. The fate of hemocytes in response to Plasmodium infection was investigated by labeling this cell population in vivo. We found that midgut nitration triggers the local release of hemocyte-derived microvesicles (HdMv) into the basal labyrinth of the midgut...
January 2017: Science Immunology
https://www.readbyqxmd.com/read/28736583/microrna-profiling-of-ovarian-granulosa-cell-tumours-reveals-novel-diagnostic-and-prognostic-markers
#9
Wei-Tzu Cheng, Roseanne Rosario, Anita Muthukaruppan, Michelle K Wilson, Kathryn Payne, Peter C Fong, Andrew N Shelling, Cherie Blenkiron
BACKGROUND: The aim of this study was to explore the clinical utility of microRNAs (miRNAs) as improved markers of ovarian granulosa cell tumours (GCTs) for cancer diagnosis and prognosis prediction. Current histopathological and genetic markers, such as the presence of a FOXL2 gene mutation to distinguish between the two major subtypes are not wholly accurate and as such novel biomarkers are warranted. METHODS: The miRNA expression profiles of five formalin-fixed, paraffin-embedded (FFPE) adult-GCTs and five juvenile-GCTs were assessed using Affymetrix miRNA 3...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28736532/a-memory-of-early-life-physical-activity-is-retained-in-bone-marrow-of-male-rats-fed-a-high-fat-diet
#10
Dharani M Sontam, Mark H Vickers, Elwyn C Firth, Justin M O'Sullivan
Studies have reported opposing effects of high-fat (HF) diet and mechanical stimulation on lineage commitment of the bone marrow stem cells. Yet, how bone marrow modulates its gene expression in response to the combined effects of mechanical loading and a HF diet has not been addressed. We investigated whether early-life (before onset of sexual maturity at 6 weeks of age) voluntary physical activity can modulate the effects of a HF diet on male Sprague Dawley rats. In the bone marrow, early-life HF diet resulted in adipocyte hypertrophy and a pro-inflammatory and pro-adipogenic gene expression profile...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28736365/-blighted-ovum-in-subfertile-patients-undergoing-assisted-reproductive-technology
#11
Qing-Wen Nie, Rui Hua, Yao Zhou, Hong Li, Yan-Hong Yu
OBJECTIVE: To explore the incidence and risk factors of blighted ovum in subfertile patients undergoing assisted reproductive technology (ART). METHODS: This retrospective analysis was conducted among 2378 patients who were pregnant following embryo transfer at our center from January, 2012 to December, 2015, including cases of early pregnancy losses and simultaneous live births. The cases with early pregnancy losses were divided into embryonic pregnancy and blighted ovum groups based on the presence or absence of an embryonic pole before dilation and curettage...
July 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28736226/rapid-effects-of-the-aromatase-inhibitor-fadrozole-on-steroid-production-and-gene-expression-in-the-ovary-of-female-fathead-minnows-pimephales-promelas
#12
Anthony L Schroeder, Gerald T Ankley, Tanwir Habib, Natalia Garcia-Reyero, Barbara L Escalon, Kathleen M Jensen, Michael D Kahl, Elizabeth J Durhan, Elizabeth A Makynen, Jenna E Cavallin, Dalma Martinovic-Weigelt, Edward J Perkins, Daniel L Villeneuve
Cytochrome P450 aromatase catalyzes conversion of C19 androgens to C18 estrogens and is critical for normal reproduction in female vertebrates. Fadrozole is a model aromatase inhibitor that has been shown to suppress estrogen production in the ovaries of fish. However, little is known about the early impacts of aromatase inhibition on steroid production and gene expression in fish. Adult female fathead minnows (Pimephales promelas) were exposed via water to 0, 5, or 50 µg fadrozole/L for a time-course of 0...
July 20, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28736181/succinate-accumulation-impairs-cardiac-pyruvate-dehydrogenase-activity-through-grp91-dependent-and-independent-signaling-pathways-therapeutic-effects-of-ginsenoside-rb1
#13
Jia Li, Yi-Lin Yang, Lan-Zhu Li, Lei Zhang, Qun Liu, Kang Liu, Ping Li, Baolin Liu, Lian-Wen Qi
Altered mitochondrial oxidation increases vulnerability to cardiac ischemia/reperfusion (I/R) injury in metabolic disorders. However, the metabolic signaling responsible for the dysfunction remains partly unknown. We sought to test whether or not hypoxic succinate accumulation could inhibit pyruvate dehydrogenase (PDH) activity and subsequently aggravate I/R injury. Results showed that saturated fatty acid palmitate stimulation increased fatty acid oxidation and induced hypoxia in cardiomyocytes, leading to succinate accumulation...
July 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28736172/early-integration-of-temperature-and-humidity-stimuli-in-the-drosophila-brain
#14
Dominic D Frank, Anders Enjin, Genevieve C Jouandet, Emanuela E Zaharieva, Alessia Para, Marcus C Stensmyr, Marco Gallio
The Drosophila antenna contains receptor neurons for mechanical, olfactory, thermal, and humidity stimuli. Neurons expressing the ionotropic receptor IR40a have been implicated in the selection of an appropriate humidity range [1, 2], but although previous work indicates that insect hygroreceptors may be made up by a "triad" of neurons (with a dry-, a cold-, and a humid-air-responding cell [3]), IR40a expression included only cold- and dry-air cells. Here, we report the identification of the humid-responding neuron that completes the hygrosensory triad in the Drosophila antenna...
July 13, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28735903/genetics-of-non-syndromic-childhood-obesity-and-the-use-of-high-throughput-dna-sequencing-technologies
#15
REVIEW
Ana Carolina Proença da Fonseca, Claudio Mastronardi, Angad Johar, Mauricio Arcos-Burgos, Gilberto Paz-Filho
BACKGROUND: Childhood obesity is a serious public health problem associated with the development of several chronic diseases, such as type 2 diabetes mellitus, dyslipidemia, and hypertension. The elevated prevalence of obesity is mostly due to inadequate diet and lifestyle, but it is also influenced by genetic factors. OBJECTIVES: To review recent advances in the field of the genetics of obesity. We summarize the list of genes associated with the rare non-syndromic forms of obesity, and explain their function...
June 16, 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28735853/a-comparative-study-of-genome-organization-and-epigenetic-mechanisms-in-model-ciliates-with-an-emphasis-on-tetrahymena-paramecium-and-oxytricha
#16
REVIEW
Yurui Wang, Yuanyuan Wang, Yalan Sheng, Jie Huang, Xiao Chen, Khaled A S Al-Rasheid, Shan Gao
As a group of unicellular eukaryotes, ciliates offer a unique system to explore epigenetic regulation, mostly due to their nuclear dualism. Ciliates launched a successful radiation after their early evolutionary branching, therefore harboring an unexpectedly rich pool of diverse biological functions and mechanisms. In this review, we compare distinct features of different ciliates in mating type determination, genome organization, DNA methylation, and removal of internal eliminated sequences (IES), with emphasis on Tetrahymena, Paramecium and Oxytricha...
July 1, 2017: European Journal of Protistology
https://www.readbyqxmd.com/read/28735517/metallothionein-expression-and-synthesis-in-the-testis-of-the-lizard-podarcis-sicula-under-natural-conditions-and-following-estrogenic-exposure
#17
Mariailaria Verderame, Ermelinda Limatola, Rosaria Scudiero
Metallothionein (MT) is the main protein involved in the homeostasis of metallic micronutrients and in cellular defence against heavy metals and reactive oxygen species. Found in almost all vertebrate tissues, MT presence and localization in the testis has been controversial. In the present study, by using in situ hybridization and immunohistochemical analysis we assessed the localization of both MT transcript and protein in Podarcis sicula testes during two different phases of the reproductive cycle: the autumnal resumption and the spring-early summer mating period...
May 3, 2017: European Journal of Histochemistry: EJH
https://www.readbyqxmd.com/read/28735504/low-genetic-diversity-and-functional-constraint-of-mirna-genes-participating-pollen-pistil-interaction-in-rice
#18
Kun Wang, Xin Wang, Ming Li, Tao Shi, Pingfang Yang
In this study, we sequenced and analyzed the expression and evolution of rice miRNA genes participating pollen-pistil interaction that is crucial to rice yield. Pollen-pistil interaction is an essential reproductive process for all flowering plants. While microRNAs (miRNAs) are important noncoding small RNAs that regulate mRNA levels in eukaryotic cells, there is little knowledge about which miRNAs involved in the early stages of pollen-pistil interaction in rice and how they evolve under this conserved process...
July 22, 2017: Plant Molecular Biology
https://www.readbyqxmd.com/read/28735299/identification-of-the-first-dominant-mutation-of-lama5-gene-causing-a-complex-multisystem-syndrome-due-to-dysfunction-of-the-extracellular-matrix
#19
Simone Sampaolo, Filomena Napolitano, Alfonsina Tirozzi, Mafalda Giovanna Reccia, Luca Lombardi, Olimpia Farina, Adriano Barra, Ferdinando Cirillo, Mariarosa Anna Beatrice Melone, Fernando Gianfrancesco, Giuseppe Di Iorio, Teresa Esposito
BACKGROUND: The laminin alpha 5 gene (LAMA5) plays a master role in the maintenance and function of the extracellular matrix (ECM) in mammalian tissues, which is critical in developmental patterning, stem cell niches, cancer and genetic diseases. Its mutations have never been reported in human disease so far. The aim of this study was to associate the first mutation in LAMA5 gene to a novel multisystem syndrome. METHODS: A detailed characterisation of a three-generation family, including clinical, biochemical, instrumental and morphological analysis, together with genetics and expression (WES and RNAseq) studies, was performed...
July 22, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/28735145/metabolic-gene-targeted-monitoring-of-non-starter-lactic-acid-bacteria-during-cheese-ripening
#20
Alessia Levante, Francesca De Filippis, Antonietta La Storia, Monica Gatti, Erasmo Neviani, Danilo Ercolini, Camilla Lazzi
Long ripened cheeses, such as Grana Padano (GP), a Protected Designation of Origin (PDO) Italian cheese, harbor a viable microbiota mainly composed of non-starter lactic acid bacteria (NSLAB), which contribute to the final characteristics of cheese. The NSLAB species Lactobacillus rhamnosus, Lb. casei and Lb. paracasei are frequently found in GP, and form a closely related taxonomic group (Lb. casei group), making it difficult to distinguish the three species through 16S rRNA sequencing. SpxB, a metabolic gene coding for pyruvate oxidase in Lb...
July 6, 2017: International Journal of Food Microbiology
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