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| Open AccessBlimp1 regulates the transition of neonatal to adult intestinal epithelium
Many mammals are born with an immature intestinal epithelium, which adapts to a changing diet during the weaning period. Muncanet al. show that the transcriptional repressor Blimp1is expressed in the intestine of mice at birth, and that expression is lost at the transition to the weaning stage.
- Vanesa Muncan
- , Jarom Heijmans
- & Gijs R. van den Brink
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Article
| Open AccessA stem-group cnidarian described from the mid-Cambrian of China and its significance for cnidarian evolution
The origin of Cnidaria—coral and jellyfish—is still unsolved in the basal metazoan phylogeny. Here, a Cambrian fossil of a stem-group cnidarian,Cambroctoconus orientalisgen. et sp. nov., is found to bear octoradial symmetry, but no jelly-like mesenchyme, suggesting this evolved after octoradial symmetry.
- Tae-yoon Park
- , Jusun Woo
- & Duck K. Choi
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Discovery of lost diversity of paternal horse lineages using ancient DNA
Modern female horses are genetically diverse but male horses are relatively homogenous. Lippoldet al. sequence the Y chromosome of nine ancient horses and detect diversity in the ancestral paternal lineage, demonstrating ancient Y-chromosomal DNA sequencing can provide insights into evolution.
- Sebastian Lippold
- , Michael Knapp
- & Michael Hofreiter
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Article
| Open AccessMesozoic retroposons reveal parrots as the closest living relatives of passerine birds
Zebra finches are passerine birds, but their phylogenetic relationship with non-passerine birds remains controversial. By examining retroposon insertion loci in avian genomes, the authors reveal that parrots are the closest relatives of passerines, which may have implications for understanding the evolution of birdsong.
- Alexander Suh
- , Martin Paus
- & Jürgen Schmitz
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Critical roles for EphB and ephrin-B bidirectional signalling in retinocollicular mapping
How retinoganglion cell axons project correctly to the superior colliculus is poorly understood. Here, projections are shown to require EphB1, EphB2 and ephrin-B1 to terminate in the medial superior colliculus, while ephrin-B2 is essential for the mapping of both dorsal and ventral axons.
- Sonal Thakar
- , George Chenaux
- & Mark Henkemeyer
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Insights into bird wing evolution and digit specification from polarizing region fate maps
Bird wings resemble the digits on the hands of dinosaurs, but which digit positions gave rise to those seen in modern birds is still unclear. In this work, long-term fate maps of the chick wing polarizing region are presented, supporting fossil data that birds descended from theropods that had digits 1, 2 and 3.
- Matthew Towers
- , Jason Signolet
- & Cheryll Tickle
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Article
| Open AccessCytosine methylation regulates oviposition in the pathogenic blood fluke Schistosoma mansoni
The chronic disease schistosomiasis is caused by the blood flukeSchistosoma mansoni. By studying DNA modifications throughout the lifecycle of the pathogen, the authors identify DNA methylation as a factor in egg development and suggest that the epigenetic machinery responsible may be a therapeutic target.
- Kathrin K. Geyer
- , Carlos M. Rodríguez López
- & Karl F. Hoffmann
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Relative comparisons of call parameters enable auditory grouping in frogs
Male túngara frogs produce overlapping mating calls, which poses a challenge for the female frog to group and assign multiple auditory signals to the correct source. Farris and Ryan shows that, like humans, the female frogs compare and group signals using the smallest relative difference in call parameters.
- Hamilton E. Farris
- & Michael J. Ryan
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Article
| Open AccessFunctional and molecular interactions between ERK and CHK2 in diffuse large B-cell lymphoma
Chk2 is a kinase that is a potential chemotherapeutic target. Here, Chk2 and the kinase ERK are shown to functionally interact, and are elevated in expression in human diffuse B-cell lymphomas. Combinatorial inhibition of the kinases was also shown to block tumour growth in anin vivomouse model.
- Bojie Dai
- , X. Frank Zhao
- & Ronald B. Gartenhaus
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The Wnt3a/β-catenin target gene Mesogenin1 controls the segmentation clock by activating a Notch signalling program
During development, Wnt-mediated Notch signalling controls the generation of somites from the presomitic mesoderm, but the precise signalling mechanism is unknown. Here, the transcription factor Mesogenin 1 is shown to be a direct target of Wnt3a and regulates the transcription of a Notch signalling program.
- Ravindra B. Chalamalasetty
- , William C. Dunty Jr
- & Terry P. Yamaguchi
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TorsinA participates in endoplasmic reticulum-associated degradation
The torsinA protein localizes to the endoplasmic reticulum and, when mutated, causes early onset torsion dystonia. The authors reveal a new role for torsinA in proteosome-mediated degradation of misfolded proteins, and relate this to endoplasmic reticulum stress, in aCaenorhabditis elegansmodel and patient fibroblasts.
- Flávia C. Nery
- , Ioanna A. Armata
- & Xandra O. Breakefield
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A photoconvertible fluorescent reporter to track chaperone-mediated autophagy
Soluble cytosolic proteins can be degraded in lysosomes by chaperone-mediated autophagy, however, the current method to measure this process requires isolation of lysosomes. Now, a fluorescent reporter is described that can measure this type of autophagy in intact cells.
- Hiroshi Koga
- , Marta Martinez-Vicente
- & Ana Maria Cuervo
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Identification of the PGRMC1 protein complex as the putative sigma-2 receptor binding site
The sigma-2 receptor is used as a biomarker for tumour cell proliferation but its identity is unknown. Using a novel radiolabelled probe, the authors identify progesterone receptor membrane component 1, which is overexpressed in several tumour types, as the putative sigma-2 receptor.
- Jinbin Xu
- , Chenbo Zeng
- & Robert H. Mach
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Pyrimidine pool imbalance induced by BLM helicase deficiency contributes to genetic instability in Bloom syndrome
Mutations in the DNA helicaseBLM cause Bloom syndrome, which is characterized by slow replication fork progression and genetic instability. Here, cells lacking BLMare shown to have a defect in cytidine deaminase, which alters the pyrimidine pool and results in replication fork progression with altered velocity.
- Pauline Chabosseau
- , Géraldine Buhagiar-Labarchède
- & Mounira Amor-Guéret
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TRPV3 regulates nitric oxide synthase-independent nitric oxide synthesis in the skin
Nitric oxide can be produced by nitric oxide synthase or by nitrite reduction, but whether the latter occurs inside cells is unknown. Here, the TRPV3 ion channel is shown to induce nitrite-dependent nitric oxide production in keratinocytes, where it has a role in thermosensory behaviour and wound healing.
- Takashi Miyamoto
- , Matt J. Petrus
- & Ardem Patapoutian
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Cyclin B-dependent kinase 1 regulates human TRF1 to modulate the resolution of sister telomeres
TRF1 is a telomere binding protein involved in sister telomere cohesion. In this study, the ability of TRF1 to bind to telomeres in mitosis is inhibited by cyclin-dependent kinase 1-mediated phosphorylation, which may facilitate sister telomere resolution during mitosis.
- Megan McKerlie
- & Xu-Dong Zhu
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Convergent evolution in locomotory patterns of flying and swimming animals
Undulating flight, an efficient mode of locomotion in flying birds, can theoretically also result in efficient locomotion in water. Here we demonstrate gait patterns resembling undulating flight in four marine vertebrate species comprising sharks and pinnipeds.
- Adrian C. Gleiss
- , Salvador J. Jorgensen
- & Rory P. Wilson
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Article
| Open AccessNeural coding in a single sensory neuron controlling opposite seeking behaviours in Caenorhabditis elegans
The neuronal mechanisms responsible for thermal seeking behaviour inCaenorhabditis. elegansare not fully understood. In this study, the sensory neuron AFD is shown to be involved in the responses to both cold and warm temperatures by transmitting inhibitory and excitatory signals to the interneuron AIY.
- Atsushi Kuhara
- , Noriyuki Ohnishi
- & Ikue Mori
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Contemporary and historical separation of transequatorial migration between genetically distinct seabird populations
Migratory segregation presents a hypothesized barrier to gene flow among seabirds, but its mechanisms are unclear. Rayneret al. find that migratory habitat specialization, associated with breeding asynchrony and philopatry, restricts gene flow between two seabird populations migrating across the Pacific Ocean.
- Matt J. Rayner
- , Mark E. Hauber
- & Scott A. Shaffer
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Article
| Open AccessGenetics and the environment converge to dysregulate N-glycosylation in multiple sclerosis
Complex diseases such as multiple sclerosis have both genetic and environmental components. This study demonstrates that variants of genes implicated in multiple sclerosis, and alterations in cellular metabolism and vitamin D3 levels, alterN-glycosylation, a post-translational modification causal of the disease in mice.
- Haik Mkhikian
- , Ani Grigorian
- & Michael Demetriou
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An evolutionarily conserved three-dimensional structure in the vertebrate Irx clusters facilitates enhancer sharing and coregulation
TheIrx genes are arranged in clusters and the reason for this arrangement is unclear. Using a chromatin conformation capture assay, the authors show that Irx genes share enhancer elements, suggesting that the gene cluster is required for coregulation of the Irxgenes.
- Juan J. Tena
- , M. Eva Alonso
- & José Luis Gómez-Skarmeta
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α-Mannosidase 2C1 attenuates PTEN function in prostate cancer cells
PTEN is a phosphatase that regulates the phosphatidylinositol-3 kinase signalling pathway and is inactivated in many tumour types. Heet al.show that a mannosidase, α-mannosidase 2C1, can inactivate PTEN in prostate cancer cells, and that PTEN-positive human prostate tumours overexpress α-mannosidase 2C1.
- Lizhi He
- , Catherine Fan
- & Damu Tang
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Article
| Open AccessRespiratory distress and perinatal lethality in Nedd4-2-deficient mice
In vitrostudies have suggested that the ubiquitin ligase, Nedd4-2, regulates several proteins, including the epithelial sodium channel. Here by examining Nedd4-2-deficient mice, the authors demonstrate that Nedd4-2 is essential for epithelial sodium channel regulation, fetal and postnatal lung function and animal survival.
- Natasha A. Boase
- , Grigori Y. Rychkov
- & Sharad Kumar
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Article
| Open AccessConvergent evolution in biosynthesis of cyanogenic defence compounds in plants and insects
Cyanide-releasing defence systems in plants and animals are important to the evolution of plant–herbivore interactions. The authors identify the enzymes responsible for biosynthesis of cyanogenic glucosides by Six-spot Burnet moth caterpillars, which have evolved independently from the known plant pathway.
- Niels Bjerg Jensen
- , Mika Zagrobelny
- & Søren Bak
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Article
| Open AccessThe global distribution of the Duffy blood group
The global prevalence of the Duffy blood group variants is important due to the resistance that the Duffy-negative phenotype generally confers uponPlasmodium vivax infection. Hay et al.generate global frequency maps of the common Duffy alleles to show transmission patterns of the malaria parasite.
- Rosalind E. Howes
- , Anand P. Patil
- & Simon I. Hay
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Article
| Open AccessIntestinal epithelial stem cells do not protect their genome by asymmetric chromosome segregation
It has been proposed that stem cells use nonrandom chromosome segregation to avoid the accumulation of replication-induced mutations. Here, the authors examine intestinal epithelial stem cell division and show, using label exclusion and retention assays, that the cells segregate their chromosomes randomly.
- Marion Escobar
- , Pierre Nicolas
- & Catherine Legraverend
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Wwp2 is essential for palatogenesis mediated by the interaction between Sox9 and mediator subunit 25
Sox9 is an important transcription factor in the formation of cartilage chondrogenesis that occurs during skeletal development. Nakamuraet al.show that Sox9 interacts with Wwp2 and Med25 to form a complex and that loss of either protein in zebrafish results in altered palate chondrogenesis.
- Yukio Nakamura
- , Koji Yamamoto
- & Haruhiko Akiyama
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Article
| Open AccessComparative transcriptome analysis reveals vertebrate phylotypic period during organogenesis
The conservation of embryonic development across species is of great interest in evolutionary biology. Here, using transcriptome analysis, the authors show that the pharyngula stage of development—in mid-embryogenesis—is conserved between mice, chickens, frogs and zebrafish.
- Naoki Irie
- & Shigeru Kuratani
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5-Hydroxymethylcytosine in the mammalian zygote is linked with epigenetic reprogramming
Pronucleus DNA becomes demethylated during zygotic development. Here, the authors demonstrate that the reduction in 5-methylcytosine levels is accompanied by an increase in the presence of 5-hydroxymethylcytosine, and suggest that this has a role in developmental reprogramming.
- Mark Wossidlo
- , Toshinobu Nakamura
- & Jörn Walter
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Larger mitochondrial DNA than Y-chromosome differences between matrilocal and patrilocal groups from Sumatra
Matrilocal and patrilocal populations are predicted to have greater genetic diversity in mitochondrial DNA and the Y-chromosome, respectively. Here, no difference in the diversity of the Y-chromosome was found in two such groups, suggesting that local diversity was caused by male gene flow in expanding populations.
- Ellen Dröfn Gunnarsdóttir
- , Madhusudan R. Nandineni
- & Mark Stoneking
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Human TSC2-null fibroblast-like cells induce hair follicle neogenesis and hamartoma morphogenesis
Mutations inTSC2 lead to the formation of benign tumours called hamartomas. In this study, using a mouse xenograft model, the authors demonstrate that fibroblasts from patients carrying TSC2mutations can induce keratinocytes to form both hair follicles and hamartoma-like growths with active mTOR signalling.
- Shaowei Li
- , Rajesh L. Thangapazham
- & Thomas N. Darling
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Coastal pollution limits pelagic larval dispersal
Storm water runoff and wastewater effluent are discharged into oceans, but the full ecological effects of these discharges are unknown. Here, the authors examine the population structure of a marine organism, the bat star, and show that these discharges alter the genetic structure and larval dispersal of this species.
- Jonathan B. Puritz
- & Robert J. Toonen
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Article
| Open AccessGipc3 mutations associated with audiogenic seizures and sensorineural hearing loss in mouse and human
Progressive sensorineural hearing loss affects many people, but the underlying genetics remain largely undefined. Here, the authors identify mutations inGIPC3in mice and two consanguineous families that lead to hearing loss and in mice cause defects in the structure of stereocilia bundles and audiogenic seizures.
- Nikoletta Charizopoulou
- , Andrea Lelli
- & Konrad Noben-Trauth
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Article
| Open AccessEffector diversification within compartments of the Leptosphaeria maculans genome affected by Repeat-Induced Point mutations
Leptosphaeria maculans is a plant pathogen that causes stem canker of oilseed rape. Rouxel et al. sequence and describe the key features of the L. maculansgenome, including partitioning into AT-rich blocks that are enriched in effector genes and transposable elements affected by repeat-induced point mutation.
- Thierry Rouxel
- , Jonathan Grandaubert
- & Barbara J. Howlett
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Tumour microvesicles contain retrotransposon elements and amplified oncogene sequences
Microvesicles containing RNA are released from tumour cells. Here, the authors show that microvesicles released from tumour cells in culture have amplified levels of thec-Myconcogene, which is also found in the cell of origin, suggesting that microvesicles could be used as biomarkers.
- Leonora Balaj
- , Ryan Lessard
- & Johan Skog
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An adaptive explanation for the horse-like shape of seahorses
Seahorses evolved from pipefish, which have a remarkably different body shape. Here, by examining seahorse feeding behaviour and using a mathematical model, Van Wassenberghet al. demonstrate that the head, neck and trunk posture of the seahorse allows for the effective capture of their prey.
- Sam Van Wassenbergh
- , Gert Roos
- & Lara Ferry
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Asymmetric spermatocyte division as a mechanism for controlling sex ratios
Some organisms produce unequal numbers of male and female progeny, but the mechanics of skewed of sex ratios are largely unknown. Here, the authors describe alterations in X-chromosome segregation and cytoplasmic partitioning during spermatogenesis that together explain the distorted sex ratio in a nematode species.
- Diane C. Shakes
- , Bryan J. Neva
- & Andre Pires-daSilva
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Insertion sequence-excision enhancer removes transposable elements from bacterial genomes and induces various genomic deletions
Insertion sequences are transposable elements that are found in the genomes of many bacteria. Here, the authors identify an enhancer element that results in a high frequency of excision of insertion elements, and suggest that the excision enhancer element coevolved with the insertion sequences.
- Masahiro Kusumoto
- , Tadasuke Ooka
- & Tetsuya Hayashi
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Article
| Open AccessHerpesviruses carrying a Brainbow cassette reveal replication and expression of limited numbers of incoming genomes
The replication of viral genomes in infected cells is required for successful infection. In this study, using Cre-conditional expression of multiple coloured fluorophores, the authors demonstrate that the number of viral genomes expressed and replicated in a cell is surprisingly limited.
- Oren Kobiler
- , Yaron Lipman
- & Lynn W. Enquist
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Article
| Open AccessSystems-wide temporal proteomic profiling in glucose-starved Bacillus subtilis
Identifying the transcripts and proteins that fluctuate in response to stimuli provides important information for understanding cell physiology. In this study, 52% of theBacillus subtilispredicted proteome is identified following glucose starvation, revealing further insight into protein dynamics at a global scale.
- Andreas Otto
- , Jörg Bernhardt
- & Dörte Becher
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Article
| Open AccessDeep resequencing reveals excess rare recent variants consistent with explosive population growth
To fully catalogue rare genetic variation in humans, many samples need to be examined. In this study, Coventryet al. resequenced two genes, KCNJ11 and HHEX, in 13,715 humans, and concluded that most of the sequence variation arose recently and that variation is greater than expected.
- Alex Coventry
- , Lara M. Bull-Otterson
- & Charles F. Sing
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Article
| Open AccessNew approach for rice improvement using a pleiotropic QTL gene for lodging resistance and yield
Much effort has been devoted to the generation of rice plants with short stature to improve grain yield and increased resistance to lodging. Through quantitative trait analysis, these authors identify a gene—STRONG CULM2—that confers increased grain yield, culm strength and spikelet number in rice.
- Taiichiro Ookawa
- , Tokunori Hobo
- & Makoto Matsuoka
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| Open AccessDisruption of TBP-2 ameliorates insulin sensitivity and secretion without affecting obesity
Thioredoxin binding protein-2 (TBP-2) mutant mice have abnormal insulin sensitivity and secretion. In this study, TBP-2-null obese mice are shown to have improved insulin sensitivity and glucose intolerance, suggesting a potential role for TBP-2 inhibition in diabetes treatment.
- Eiji Yoshihara
- , Shimpei Fujimoto
- & Hiroshi Masutani
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Article
| Open AccessA β-synuclein mutation linked to dementia produces neurodegeneration when expressed in mouse brain
Little is known about β-synuclein mutations in neurological disease. In this article, the authors demonstrate that mice with a mutation in β-synuclein show progressive neurodegenerative disease and suggest that this mutation can enhance the brain defects caused by α-synuclein mutations in mice.
- Masayo Fujita
- , Shuei Sugama
- & Makoto Hashimoto
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| Open AccessTectorial membrane travelling waves underlie abnormal hearing in Tectb mutant mice
Mutation of theTectbgene reduces auditory sensitivity but increases frequency selectivity. Here the authors show that Tectb mutation reduces both the spatial and temporal propagation of travelling waves along the tectorial membrane, explaining the unexpected auditory abnormalities in this mutant.
- Roozbeh Ghaffari
- , Alexander J. Aranyosi
- & Dennis M. Freeman
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G-protein β2 subunit interacts with mitofusin 1 to regulate mitochondrial fusion
Little is known about the regulation of mitofusin proteins that are involved in the fusion of mitochondrial membranes. In this study, the authors report that a heterotrimeric G protein, Gβ-subunit 2, can interact with mitofusin 1, and is involved in the regulation of mitochondrial fusion.
- Juan Zhang
- , Weihua Liu
- & Quan Chen
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Article
| Open AccessDynamic evolution of precise regulatory encodings creates the clustered site signature of enhancers
InDrosophila development, DNA enhancers drive gene expression in response to morphogen gradients. Here, Crocker et al. study the evolution of sequences that bind a Dorsal morphogen complex and demonstrate how evolutionary changes in threshold levels have resulted in complex site clustering of DNA elements.
- Justin Crocker
- , Nathan Potter
- & Albert Erives
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Development of a novel selective inhibitor of the Down syndrome-related kinase Dyrk1A
The kinase Dyrk1A is essential for brain function and development, and its excessive activity has been implicated in Down syndrome. In this study, a selective inhibitor of Dyrk1A is developed, which may help to elucidate the molecular mechanisms of normal and diseased brain.
- Yasushi Ogawa
- , Yosuke Nonaka
- & Masatoshi Hagiwara
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Article
| Open AccessThe complete sequence of the smallest known nuclear genome from the microsporidian Encephalitozoon intestinalis
A comparison of related genomes provides valuable information about how they evolve. Here, the complete sequence of the smallest known nuclear genome from the microsporidiaE. intestinalis is described and compared with its larger sister E. cuniculi, revealing what parts are indispensable in even the most reduced genomes.
- Nicolas Corradi
- , Jean-François Pombert
- & Patrick J. Keeling
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