scholarly journals Hedgehog signaling controls segmentation dynamics and diversity via msx1 in a spider embryo

2020 ◽  
Vol 6 (37) ◽  
pp. eaba7261
Author(s):  
Yasuko Akiyama-Oda ◽  
Hiroki Oda
Keyword(s):  
Hedgehog Signaling ◽  
The Body ◽  
Body Region ◽  
Altered States ◽  
Genome Wide ◽  
Body Patterning ◽  
Genome Wide Data ◽  
Hh Signaling ◽  
Anterior Posterior

Hedgehog (Hh) signaling plays fundamental roles in animal body patterning. Understanding its mechanistic complexity requires simple tractable systems that can be used for these studies. In the early spider embryo, Hh signaling mediates the formation of overall anterior-posterior polarity, yet it remains unclear what mechanisms link the initial Hh signaling activity with body axis segmentation, in which distinct periodic stripe-forming dynamics occur depending on the body region. We performed genome-wide searches for genes that transcriptionally respond to altered states of Hh signaling. Characterization of genes negatively regulated by Hh signaling suggested that msx1, encoding a conserved transcription factor, functions as a key segmentation gene. Knockdown of msx1 prevented all dynamic processes causing spatial repetition of stripes, including temporally repetitive oscillations and bi-splitting, and temporally nonrepetitive tri-splitting. Thus, Hh signaling controls segmentation dynamics and diversity via msx1. These genome-wide data from an invertebrate illuminate novel mechanistic features of Hh-based patterning.

Role of knot (kn) in Wing Patterning in Drosophila

Genetics ◽  
1997 ◽  
Vol 147 (3) ◽  
pp. 1203-1212 ◽  
Author(s):  
Katerina Nestoras ◽  
Helena Lee ◽  
Jym Mohler
Keyword(s):  
Hedgehog Signaling ◽  
Imaginal Disc ◽  
Hedgehog Signaling Pathway ◽  
Posterior Compartment ◽  
Drosophila Wing ◽  
Compartment Boundary ◽  
Hh Signaling ◽  
Embryonic Segmentation ◽  
Anterior Posterior

We have undertaken a genetic analysis of new strong alleles of knot (kn). The original kn1 mutation causes an alteration of wing patterning similar to that associated with mutations of fused (fu), an apparent fusion of veins 3 and 4 in the wing. However, unlike fu, strong kn mutations do not affect embryonic segmentation and indicate that kn is not a component of a general Hh (Hedgehog)-signaling pathway. Instead we find that kn has a specific role in those cells of the wing imaginal disc that are subject to ptc-mediated Hh-signaling. Our results suggest a model for patterning the medial portion of the Drosophila wing, whereby the separation of veins 3 and 4 is maintained by kn activation in the intervening region in response to Hh-signaling across the adjacent anterior-posterior compartment boundary.

scholarly journals Hedgehog signaling enables nutrition-responsive inhibition of an alternative morph in a polyphenic beetle

2016 ◽  
Vol 113 (21) ◽  
pp. 5982-5987 ◽  
Author(s):  
Teiya Kijimoto ◽  
Armin P. Moczek
Keyword(s):  
Signaling Pathway ◽  
Hedgehog Signaling ◽  
Developmental Evolution ◽  
Genetic Components ◽  
Alternative Phenotypes ◽  
Novel Traits ◽  
Hh Signaling ◽  
Linear State ◽  
Horned Beetles ◽  
Anterior Posterior

The recruitment of modular developmental genetic components into new developmental contexts has been proposed as a central mechanism enabling the origin of novel traits and trait functions without necessitating the origin of novel pathways. Here, we investigate the function of the hedgehog (Hh) signaling pathway, a highly conserved pathway best understood for its role in patterning anterior/posterior (A/P) polarity of diverse traits, in the developmental evolution of beetle horns, an evolutionary novelty, and horn polyphenisms, a highly derived form of environment-responsive trait induction. We show that interactions among pathway members are conserved during development of Onthophagus horned beetles and have retained the ability to regulate A/P polarity in traditional appendages, such as legs. At the same time, the Hh signaling pathway has acquired a novel and highly unusual role in the nutrition-dependent regulation of horn polyphenisms by actively suppressing horn formation in low-nutrition males. Down-regulation of Hh signaling lifts this inhibition and returns a highly derived sigmoid horn body size allometry to its presumed ancestral, linear state. Our results suggest that recruitment of the Hh signaling pathway may have been a key step in the evolution of trait thresholds, such as those involved in horn polyphenisms and the corresponding origin of alternative phenotypes and complex allometries.

scholarly journals BlackSheep: A Bioconductor and Bioconda package for differential extreme value analysis

2019 ◽  
Author(s):  
Lili Blumenberg ◽  
Emily Kawaler ◽  
MacIntosh Cornwell ◽  
Shaleigh Smith ◽  
Kelly Ruggles ◽  
...  
Keyword(s):  
Differential Expression Analysis ◽  
Shotgun Proteomics ◽  
Small Sample ◽  
Extreme Value Analysis ◽  
Differential Analysis ◽  
Value Analysis ◽  
Genome Wide ◽  
Genome Wide Data ◽  
Parametric Description

AbstractUnbiased assays such as shotgun proteomics and RNA-seq provide high-resolution molecular characterization of tumors. These assays measure molecules with highly varied distributions, making interpretation and hypothesis testing challenging. Samples with the most extreme measurements for a molecule can reveal the most interesting biological insights, yet are often excluded from analysis. Furthermore, rare disease subtypes are, by definition, underrepresented in cancer cohorts. To provide a strategy for identifying molecules aberrantly enriched in small sample cohorts, we present BlackSheep--a package for non-parametric description and differential analysis of genome-wide data, available at https://github.com/ruggleslab/blackSheep. BlackSheep is a complementary tool to other differential expression analysis methods that may be underpowered when analyzing small subgroups in a larger cohort.

scholarly journals A comprehensive portrait of cilia and ciliopathies from a CRISPR-based screen for Hedgehog signaling

2017 ◽  
Author(s):  
David K. Breslow ◽  
Sascha Hoogendoorn ◽  
Adam R. Kopp ◽  
David W. Morgens ◽  
Brandon K. Vu ◽  
...  
Keyword(s):  
Hedgehog Signaling ◽  
Heart Defects ◽  
Functional Genomic ◽  
False Negatives ◽  
Systematic Analysis ◽  
Ciliary Function ◽  
Genome Wide ◽  
Ciliary Signaling ◽  
Selection Of

AbstractThe primary cilium organizes Hedgehog signaling, shapes embryonic development and is the unifying cause of the ciliopathies. We conducted a functional genomic screen for Hedgehog signaling by engineering antibiotic-based selection of Hedgehog-responsive cells and applying genome-wide CRISPR-mediated gene disruption. The screen robustly identifies factors required for ciliary signaling with few false positives or false negatives. Characterization of hit genes uncovers novel components of several ciliary structures including a protein complex containing ε- and δ- tubulin that is required for centriole maintenance. The screen also provides an unbiased tool for classifying ciliopathies and reveals that many forms of congenital heart defects are ciliopathies. Collectively, this screen enables a systematic analysis of ciliary function and of ciliopathies and also defines a versatile platform for dissecting signaling pathways through CRISPR-based screening.

Hedgehog signaling and the axial patterning of Drosophila wings

2000 ◽  
Vol 78 (5) ◽  
pp. 585-591 ◽  
Author(s):  
William J Brook
Keyword(s):  
Signal Transduction ◽  
Cell Fate ◽  
Limb Development ◽  
Hedgehog Signaling ◽  
Post Translational Modification ◽  
Cubitus Interruptus ◽  
Axial Patterning ◽  
Correct Location ◽  
Hh Signaling ◽  
Anterior Posterior

Growth and cell fate in the anterior-posterior (A/P) axis of the developing wing of Drosophila melanogaster are controlled by a stripe of cells bisecting the axis called the A/P organizer. Hedgehog (Hh) signaling from posterior to anterior cells induces the organizer. Several Hh-responsive genes expressed by cells of the organizer mediate its patterning activity. The Hh-signaling pathway controls the post-translational modification of the transcription factor Cubitus-interruptus (Ci) and the resulting local activation of Ci is required for the correct location of the A/P organizer.Key words: Hedgehog, morphogen, Drosophila, limb development, signal transduction.

scholarly journals Molecular characterization of CNS paragangliomas identifies cauda equina paragangliomas as a distinct tumor entity

2020 ◽  
Vol 140 (6) ◽  
pp. 893-906
Author(s):  
Leonille Schweizer ◽  
Felix Thierfelder ◽  
Christian Thomas ◽  
Patrick Soschinski ◽  
Abigail Suwala ◽  
...  
Keyword(s):  
Cauda Equina ◽  
Genetic Alterations ◽  
The Body ◽  
Molecular Profile ◽  
Sporadic Tumor ◽  
Genome Wide ◽  
Tumor Entity ◽  
Paraganglioma Syndrome ◽  
Strong Immunoreactivity

AbstractParagangliomas/pheochromocytomas are rare neuroendocrine tumors that arise from the adrenal gland or ganglia at various sites throughout the body. They display a remarkable diversity of driver alterations and are associated with germline mutations in up to 40% of the cases. Comprehensive molecular profiling of abdomino-thoracic paragangliomas revealed four molecularly defined and clinically relevant subtypes. Paragangliomas of the cauda equina region are considered to belong to one of the defined molecular subtypes, but a systematic molecular analysis has not yet been performed. In this study, we analyzed genome-wide DNA methylation profiles of 57 cauda equina paragangliomas and show that these tumors are epigenetically distinct from non-spinal paragangliomas and other tumors. In contrast to paragangliomas of other sites, chromosomal imbalances are widely lacking in cauda equina paragangliomas. Furthermore, RNA and DNA exome sequencing revealed that frequent genetic alterations found in non-spinal paragangliomas—including the prognostically relevant SDH mutations—are absent in cauda equina paragangliomas. Histologically, cauda equina paragangliomas show frequently gangliocytic differentiation and strong immunoreactivity to pan-cytokeratin and cytokeratin 18, which is not common in paragangliomas of other sites. None of our cases had a familial paraganglioma syndrome. Tumors rarely recurred (9%) or presented with multiple lesions within the spinal compartment (7%), but did not metastasize outside the CNS. In summary, we show that cauda equina paragangliomas represent a distinct, sporadic tumor entity defined by a unique clinical and morpho-molecular profile.

scholarly journals Genetic Characterization of the Resorcinol Catabolic Pathway in Corynebacterium glutamicum

2006 ◽  
Vol 72 (11) ◽  
pp. 7238-7245 ◽  
Author(s):  
Yan Huang ◽  
Ke-Xin Zhao ◽  
Xi-Hui Shen ◽  
Muhammad Tausif Chaudhry ◽  
Cheng-Ying Jiang ◽  
...  
Keyword(s):  
Corynebacterium Glutamicum ◽  
Genetic Characterization ◽  
Gene Clusters ◽  
Sole Source ◽  
Cloning And Expression ◽  
Catabolic Pathway ◽  
E Coli ◽  
Genome Wide ◽  
Genome Wide Data

ABSTRACT Corynebacterium glutamicum grew on resorcinol as a sole source of carbon and energy. By genome-wide data mining, two gene clusters, designated NCgl1110-NCgl1113 and NCgl2950-NCgl2953, were proposed to encode putative proteins involved in resorcinol catabolism. Deletion of the NCgl2950-NCgl2953 gene cluster did not result in any observable phenotype changes. Disruption and complementation of each gene at NCgl1110-NCgl1113, NCgl2951, and NCgl2952 indicated that these genes were involved in resorcinol degradation. Expression of NCgl1112, NCgl1113, and NCgl2951 in Escherichia coli revealed that NCgl1113 and NCgl2951 both coded for hydroxyquinol 1,2-dioxygenases and NCgl1112 coded for maleylacetate reductases. NCgl1111 encoded a putative monooxygenase, but this putative hydroxylase was very different from previously functionally identified hydroxylases. Cloning and expression of NCgl1111 in E. coli revealed that NCgl1111 encoded a resorcinol hydroxylase that needs NADPH as a cofactor. E. coli cells containing Ncgl1111 and Ncgl1113 sequentially converted resorcinol into maleylacetate. NCgl1110 and NCgl2950 both encoded putative TetR family repressors, but only NCgl1110 was transcribed and functional. NCgl2953 encoded a putative transporter, but disruption of this gene did not affect resorcinol degradation by C. glutamicum. The function of NCgl2953 remains unclear.

Studies on the Characterization of Factor VIII and a Co-factor VIII

1974 ◽  
Vol 31 (02) ◽  
pp. 328-338
Author(s):  
M. M. P Paulssen ◽  
H. L. M. A Vandenbussche-Scheffers ◽  
P. B Spaan ◽  
T de Jong ◽  
M. C Planje
Keyword(s):  
Molecular Weight ◽  
Factor Viii ◽  
The Body ◽  
Haemophilia A ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Polysaccharide Content ◽  
Plasma Factor ◽  
Two Factors

SummaryFactor VIII occurs in the body in two different forms. In lymph factor VIII is bound to chylomicra. In plasma, factor VIII is bound to a protein.After delipidation of chylomicra we obtained a glycoprotein with a high polysaccharide content and a molecular weight of approx. 160,000.In plasma, factor VIII is attached to a protein which is present in normal concentrations in plasma of patients with haemophilia A and in serum (co-factor VIII).This factor is deficient in both the plasma and the serum of patients with von Willebrand’s disease.The binding between factor VIII and co-factor VIII is reversible.Some properties of these two factors are described.

The Sober Bacchae: Dance as Phenomenal Limitation in Nietzsche

2019 ◽  
Vol 37 (1) ◽  
pp. 59-76
Author(s):  
Monique Lyle
Keyword(s):  
World View ◽  
The Body ◽  
Specific Function ◽  
Alain Badiou ◽  
Classical Greece ◽  
Birth Of Tragedy

This essay seeks to dispel entrenched critical opinion regarding dance across Nietzsche's writings as representative of Dionysian intoxication alone. Taking as its prompt the riposte of Alain Badiou, ‘Nietzsche is miles away from any doctrine of dance as a primitive ecstasy’ and ‘dance is in no way the liberated bodily impulse, the wild energy of the body’, the essay uncovers the ties between dance and Apollo in the Nietzschean theory of art while qualifying dance's relation to Dionysus. Primarily through an analysis of The Dionysiac World View and The Birth of Tragedy, the essay seeks to illuminate enigmatic statements about dance in Nietzsche (‘in dance the greatest strength is only potential, although it is betrayed by the suppleness of movement’ and ‘dance is the preservation of orderly measure’). It does this through an elucidation of the specific function of dance in Nietzsche's interpretation of classical Greece; via an assessment of the difficulties associated with the Nietzschean understanding of the bacchanal; and lastly through an analysis of Nietzsche's characterization of dance as a symbol. The essay culminates in a discussion of dance's ties to Nietzschean life affirmation; here the themes of physico-phenomenal existence, joy and illusion in Nietzsche are surveyed.

In-vivo evaluation of cisplatin nanoparticles encompass natural polymer

2020 ◽  
Vol 6 (1) ◽  
pp. 1-7
Author(s):  
Bhavani J ◽  
Sunil Kumar Prajapati ◽  
Ravichandran S
Keyword(s):  
Tumor Volume ◽  
Nitrogen Mustard ◽  
Common Type ◽  
The Body ◽  
Nano Particles ◽  
Natural Polymer ◽  
Drinking Alcohol ◽  
In Vivo Evaluation

Cancer is assemblage diseases involving abnormal cell growth amid the potential of spread to other parts of the body due to tobacco use are the cause of about of cancer deaths. Another 10% is due to obesity, poor diet & drinking alcohol. In 2012 about 14.1 million new cases of cancer occurred globally. In females, the most common type is breast cancer. Cisplatin also known as cytophosphane is a nitrogen mustard alkylating agent from the oxazophosphinans groups were used to treat cancers & autoimmune disorders. Based on the above reasons I will fix the aim Preparation characterization of Cisplatin- nano particles  &  its anticancer activity. Solid tumor volume examination report showed that the assessment of different day indication 15,20,25 & 30th variations of different groups of tumor volumes were decreased CPG Nanoparticles (100 mg/kg)+ DAL(15th day 4.97±0.24↓), (20th day 0.6±0.13↓), (25th day 1.35±0.30↓) & (30th day 1.89±0.13↓).

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