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Forward genetics

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https://www.readbyqxmd.com/read/28109717/dicer-1-regulates-proliferative-potential-of-drosophila-larval-neural-stem-cells-through-bantam-mirna-based-down-regulation-of-the-g1-s-inhibitor-dacapo
#1
Animesh Banerjee, Jagat Kumar Roy
The present work elucidates the role of miRNA in cell cycle regulation during brain development in Drosophila. Here we report that lineage specific depletion of dicer-1, a classically acknowledged miRNA biogenesis protein in neuroblasts leads to a reduction in their numbers and size in the third instar larval central brain. These brains also showed lower number of mitotically active cells and when homozygous mitotic clones were generated in an otherwise heterozygous dicer-1 mutant background via MARCM technique, they showed reduced number of progeny cells in individual clones, substantiating the adverse effect of the loss of dicer-1 on the proliferative potential of neuroblasts...
January 18, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28109405/challenges-and-methodology-in-the-incorporation-of-biomarkers-in-cancer-clinical-trials
#2
REVIEW
Charlotte S Wilhelm-Benartzi, Shahrul Mt-Isa, Francesca Fiorentino, Robert Brown, Deborah Ashby
Biomarkers can be used to establish more homogeneous groups using the genetic makeup of the tumour to inform the selection of treatment for each individual patient. However, proper preclinical work and stringent validation are needed before taking forward biomarkers into confirmatory studies. Despite the challenges, incorporation of biomarkers into clinical trials could better target appropriate patients, and potentially be lifesaving. The authors conducted a systematic review to describe marker-based and adaptive design methodology for their integration in clinical trials, and to further describe the associated practical challenges...
February 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28108586/fluctuating-selection-in-the-moran
#3
Antony M Dean, Clarence Lehman, Xiao Yi
Contrary to classical population genetics theory, experiments demonstrate that fluctuating selection can protect a haploid polymorphism in the absence of frequency dependent effects on fitness. Using forward simulations with the Moran model we confirm our analytical results showing that a fluctuating selection regime, with a mean selection coefficient of zero, promotes polymorphism. We find that increases in heterozygosity over neutral expectations are especially pronounced when fluctuations are rapid, mutation is weak, the population size is large and the variance in selection is big...
January 20, 2017: Genetics
https://www.readbyqxmd.com/read/28107502/rnai-based-functional-genomics-identifies-new-virulence-determinants-in-mucormycosis
#4
Trung Anh Trieu, María Isabel Navarro-Mendoza, Carlos Pérez-Arques, Marta Sanchis, Javier Capilla, Patricia Navarro-Rodriguez, Loida Lopez-Fernandez, Santiago Torres-Martínez, Victoriano Garre, Rosa María Ruiz-Vázquez, Francisco E Nicolás
Mucorales are an emerging group of human pathogens that are responsible for the lethal disease mucormycosis. Unfortunately, functional studies on the genetic factors behind the virulence of these organisms are hampered by their limited genetic tractability, since they are reluctant to classical genetic tools like transposable elements or gene mapping. Here, we describe an RNAi-based functional genomic platform that allows the identification of new virulence factors through a forward genetic approach firstly described in Mucorales...
January 20, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28106575/introduction-forecasting-informatics-competencies-for-nurses-in-the-future-of-connected-health
#5
Judy Murphy, William Goossen
This introduction to the book discusses how the topic of competencies for nurses in a world of connected health needs to be addressed at the curriculum level to achieve the specific competencies for various roles, including practicing nurse, nurse teacher, nurse leader, and nursing informatics specialists. It looks back at milestone publications from the international Nursing Informatics post conferences that still serve a purpose for inspiring developments today and looks forward to the way nurses can use connected health to improve the health and health care for their patients...
2017: Studies in Health Technology and Informatics
https://www.readbyqxmd.com/read/28105701/climate-change-and-alpine-stream-biology-progress-challenges-and-opportunities-for-the-future
#6
Scott Hotaling, Debra S Finn, J Joseph Giersch, David W Weisrock, Dean Jacobsen
In alpine regions worldwide, climate change is dramatically altering ecosystems and affecting biodiversity in many ways. For streams, receding alpine glaciers and snowfields, paired with altered precipitation regimes, are driving shifts in hydrology, species distributions, basal resources, and threatening the very existence of some habitats and biota. Alpine streams harbour substantial species and genetic diversity due to significant habitat insularity and environmental heterogeneity. Climate change is expected to affect alpine stream biodiversity across many levels of biological resolution from micro- to macroscopic organisms and genes to communities...
January 20, 2017: Biological Reviews of the Cambridge Philosophical Society
https://www.readbyqxmd.com/read/28103232/a-model-of-compound-heterozygous-loss-of-function-alleles-is-broadly-consistent-with-observations-from-complex-disease-gwas-datasets
#7
Jaleal S Sanjak, Anthony D Long, Kevin R Thornton
The genetic component of complex disease risk in humans remains largely unexplained. A corollary is that the allelic spectrum of genetic variants contributing to complex disease risk is unknown. Theoretical models that relate population genetic processes to the maintenance of genetic variation for quantitative traits may suggest profitable avenues for future experimental design. Here we use forward simulation to model a genomic region evolving under a balance between recurrent deleterious mutation and Gaussian stabilizing selection...
January 19, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28099906/genomic-characteristics-of-pancreatic-squamous-cell-carcinoma-an-investigation-by-using-high-throughput-sequencing-after-in-solution-hybrid-capture
#8
Meng-Dan Xu, Shu-Ling Liu, Yi-Zhong Feng, Qiang Liu, Meng Shen, Qiaoming Zhi, Zeyi Liu, Dong-Mei Gu, Jie Yu, Liu-Mei Shou, Fei-Ran Gong, Qi Zhu, Weiming Duan, Kai Chen, Junning Zhang, Meng-Yao Wu, Min Tao, Wei Li
Squamous cell carcinoma (SCC) of pancreas is a rare histotype of pancreatic ductal carcinoma which is distinct from pancreatic adenocarcinoma (AC). Although there are standard treatments for pancreatic AC, no precise therapies exist for pancreatic SCC. Here, we screened 1033 cases of pancreatic cancer and identified 2 cases of pure SCC, which were pathologically diagnosed on the basis of finding definite intercellular bridges and/or focal keratin peal formation in the tumor cells. Immunohistochemistry assay confirmed the positive expression of CK5/6 and p63 in pancreatic SCC...
January 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28098555/nematophagous-fungus-arthrobotrys-oligospora-mimics-olfactory-cues-of-sex-and-food-to-lure-its-nematode-prey
#9
Yen-Ping Hsueh, Matthew R Gronquist, Erich M Schwarz, Ravi David Nath, Ching-Han Lee, Shalha Gharib, Frank C Schroeder, Paul W Sternberg
To study the molecular basis for predator-prey coevolution, we investigated how Caenorhabditis elegans responds to the predatory fungus Arthrobotrys oligospora. C. elegans and other nematodes were attracted to volatile compounds produced by A. oligospora. Gas-chromatographic mass-spectral analyses of A. oligospora-derived volatile metabolites identified several odors mimicking food cues attractive to nematodes. One compound, methyl 3-methyl-2-butenoate (MMB) additionally triggered strong sex- and stage-specific attraction in several Caenorhabditis species...
January 18, 2017: ELife
https://www.readbyqxmd.com/read/28096902/functional-characterization-of-the-active-mutator-like-transposable-element-muta1-from-the-mosquito-aedes-aegypti
#10
Kun Liu, Susan R Wessler
BACKGROUND: Mutator-like transposable elements (MULEs) are widespread with members in fungi, plants, and animals. Most of the research on the MULE superfamily has focused on plant MULEs where they were discovered and where some are extremely active and have significant impact on genome structure. The maize MuDR element has been widely used as a tool for both forward and reverse genetic studies because of its high transposition rate and preference for targeting genic regions. However, despite being widespread, only a few active MULEs have been identified, and only one, the rice Os3378, has demonstrated activity in a non-host organism...
2017: Mobile DNA
https://www.readbyqxmd.com/read/28096190/gain-of-function-mutants-of-the-cytokinin-receptors-ahk2-and-ahk3-regulate-plant-organ-size-flowering-time-and-plant-longevity
#11
Isabel Bartrina, Helen Jensen, Ondrej Novak, Miroslav Strnad, Tomas Werner, Thomas Schmülling
The phytohormone cytokinin is a regulator of numerous processes in plants. In Arabidopsis thaliana, the cytokinin signal is perceived by three membrane-located receptors named ARABIDOPSIS HISTIDINE KINASE2 (AHK2), AHK3 and AHK4/CRE1. How the signal is transmitted across the membrane is an entirely unknown process. The three receptors have been shown to operate mostly in a redundant fashion and only very few specific roles have been attributed to single receptors. Using a forward genetic approach, we isolated constitutively active gain-of-function variants of the AHK2 and AHK3 genes, named repressor of cytokinin deficiency2 (rock2) and rock3, respectively...
January 17, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28095622/talens-and-crispr-cas9-fuel-genetically-engineered-clinically-relevant-xenopus-tropicalis-tumor-models
#12
REVIEW
Thomas Naert, Tom van Nieuwenhuysen, Kris Vleminckx
The targeted nuclease revolution (TALENs, CRISPR/Cas9) now allows Xenopus researchers to rapidly generate custom on-demand genetic knockout models. These novel methods to perform reverse genetics are unprecedented and are fueling a wide array of human disease models within the aquatic diploid model organism Xenopus tropicalis (X. tropicalis). This emerging technology review focuses on the tools to rapidly generate genetically engineered X. tropicalis models (GEXM), with a focus on establishment of genuine genetic and clinically relevant cancer models...
January 17, 2017: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/28092281/renal-tubular-acidosis
#13
Fernando Santos, Helena Gil-Peña, Silvia Alvarez-Alvarez
PURPOSE OF REVIEW: To facilitate the understanding and knowledge of renal tubular acidosis by providing a summarized information on the known clinical and biochemical characteristics of this group of diseases, by updating the genetic and molecular bases of the primary forms renal tubular acidosis and by examining some issues regarding the diagnosis of distal renal tubular acidosis (RTA) in the daily clinical practice. RECENT FINDINGS: The manuscript presents recent findings on the potential of next-generation sequencing to disclose new pathogenic variants in patients with a clinical diagnosis of primary RTA and negative Sanger sequencing of known genes...
January 13, 2017: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/28087781/deleterious-variants-in-asian-rice-and-the-potential-cost-of-domestication
#14
Qingpo Liu, Yongfeng Zhou, Peter L Morrell, Brandon S Gaut
Many SNPs are predicted to encode deleterious amino acid variants. These slightly deleterious mutations can provide unique insights into population history, the dynamics of selection, and the genetic bases of phenotypes. This is especially true for domesticated species, where a history of bottlenecks and selection may affect the frequency of deleterious variants and signal a 'cost of domestication'. Here we investigated the numbers and frequencies of deleterious variants in Asian rice (O. sativa), focusing on two varieties (japonica and indica) and their wild relative (O...
January 12, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28087121/upper-extremity-outcome-measures-for-collagen-vi-related-myopathy-and-lama2-related-muscular-dystrophy
#15
Roxanna M Bendixen, Jocelyn Butrum, Mina S Jain, Rebecca Parks, Bonnie Hodsdon, Carmel Nichols, Michelle Hsia, Leslie Nelson, Katherine C Keller, Michelle McGuire, Jeffrey S Elliott, Melody M Linton, Irene C Arveson, Fatou Tounkara, Ruhi Vasavada, Elizabeth Harnett, Monal Punjabi, Sandra Donkervoort, Jahannaz Dastgir, Meganne E Leach, Anne Rutkowski, Melissa Waite, James Collins, Carsten G Bönnemann, Katherine G Meilleur
Congenital muscular dystrophy (CMD) comprises a rare group of genetic muscle diseases that present at birth or early during infancy. Two common subtypes of CMD are collagen VI-related muscular dystrophy (COL6-RD) and laminin alpha 2-related dystrophy (LAMA2-RD). Traditional outcome measures in CMD include gross motor and mobility assessments, yet significant motor declines underscore the need for valid upper extremity motor assessments as a clinical endpoint. This study validated a battery of upper extremity measures in these two CMD subtypes for future clinical trials...
December 5, 2016: Neuromuscular Disorders: NMD
https://www.readbyqxmd.com/read/28079877/genome-wide-transposon-screening-and-quantitative-insertion-site-sequencing-for-cancer-gene-discovery-in-mice
#16
Mathias J Friedrich, Lena Rad, Iraad F Bronner, Alexander Strong, Wei Wang, Julia Weber, Matthew Mayho, Hannes Ponstingl, Thomas Engleitner, Carolyn Grove, Anja Pfaus, Dieter Saur, Juan Cadiñanos, Michael A Quail, George S Vassiliou, Pentao Liu, Allan Bradley, Roland Rad
Transposon-mediated forward genetics screening in mice has emerged as a powerful tool for cancer gene discovery. It pinpoints cancer drivers that are difficult to find with other approaches, thus complementing the sequencing-based census of human cancer genes. We describe here a large series of mouse lines for insertional mutagenesis that are compatible with two transposon systems, PiggyBac and Sleeping Beauty, and give guidance on the use of different engineered transposon variants for constitutive or tissue-specific cancer gene discovery screening...
February 2017: Nature Protocols
https://www.readbyqxmd.com/read/28079861/endoscopic-vs-surgical-interventions-for-painful-chronic-pancreatitis-what-is-needed-for-future-clinical-trials
#17
REVIEW
John A Windsor, Nageshwar D Reddy
The treatment of painful chronic pancreatitis remains controversial. The available evidence from two randomized controlled trials favor surgical intervention, whereas an endotherapy-first approach is widely practiced. Chronic pancreatitis is complex disease with different genetic and environmental factors, different pain mechanisms and different treatment modalities including medical, endoscopic, and surgical. The widely practiced step-up approach remains unproven. In designing future clinical trials there are some important pre-requisites including a more comprehensive pain assessment tool, the optimization of conservative medical treatment and interventional techniques...
January 12, 2017: Clinical and Translational Gastroenterology
https://www.readbyqxmd.com/read/28077953/systematic-epistatic-mapping-of-cellular-processes
#18
EDITORIAL
Maximilian Billmann, Michael Boutros
Genetic screens have identified many novel components of various biological processes, such as components required for cell cycle and cell division. While forward genetic screens typically generate unstructured 'hit' lists, genetic interaction mapping approaches can identify functional relations in a systematic fashion. Here, we discuss a recent study by our group demonstrating a two-step approach to first screen for regulators of the mitotic cell cycle, and subsequently guide hypothesis generation by using genetic interaction analysis...
2017: Cell Division
https://www.readbyqxmd.com/read/28070290/cancer-brings-forward-oviposition-in-the-fly-drosophila-melanogaster
#19
Audrey Arnal, Camille Jacqueline, Beata Ujvari, Lucas Leger, Céline Moreno, Dominique Faugere, Aurélie Tasiemski, Céline Boidin-Wichlacz, Dorothée Misse, François Renaud, Jacques Montagne, Andreu Casali, Benjamin Roche, Frédéric Mery, Frédéric Thomas
Hosts often accelerate their reproductive effort in response to a parasitic infection, especially when their chances of future reproduction decrease with time from the onset of the infection. Because malignancies usually reduce survival, and hence potentially the fitness, it is expected that hosts with early cancer could have evolved to adjust their life-history traits to maximize their immediate reproductive effort. Despite the potential importance of these plastic responses, little attention has been devoted to explore how cancers influence animal reproduction...
January 2017: Ecology and Evolution
https://www.readbyqxmd.com/read/28067383/the-functional-consequences-and-prognostic-value-of-dosage-sensitivity-in-ovarian-cancer
#20
Zichuang Yan, Yongjing Liu, Yunzhen Wei, Ning Zhao, Qiang Zhang, Cheng Wu, Zhiqiang Chang, Yan Xu
Copy number alteration (CNA) represents an important class of genetic variations that may contribute to tumorigenesis, tumor growth and metastatic spread. CNA can directly affect the expression of genes within the CNA regions; however, genes within the CNA regions exhibit heterogeneity in gene dosage sensitivity. In this study, a computational framework was built to identify 1170 dosage-sensitive genes (DSGs) and 1215 dosage-resistant genes (DRGs) that were related to ovarian serous cystadenocarcinoma (OV) through the association between CNA and gene expression...
January 9, 2017: Molecular BioSystems
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