scholarly journals Ubx-Collier signaling cascade maintains blood progenitors in the posterior lobes of the Drosophila larval lymph gland

PLoS Genetics ◽  
2021 ◽  
Vol 17 (8) ◽  
pp. e1009709
Author(s):  
Aditya Kanwal ◽  
Pranav Vijay Joshi ◽  
Sudip Mandal ◽  
Lolitika Mandal
Keyword(s):  
Abdominal Segment ◽  
Normal Development ◽  
Lymph Gland ◽  
Signaling Cascade ◽  
Posterior Lobe ◽  
Signaling Center ◽  
Local Signaling ◽  
Mechanistic Basis

Drosophila larval hematopoiesis occurs in a specialized multi-lobed organ called the lymph gland. Extensive characterization of the organ has provided mechanistic insights into events related to developmental hematopoiesis. Spanning from the thoracic to the abdominal segment of the larvae, this organ comprises a pair of primary, secondary, and tertiary lobes. Much of our understanding arises from the studies on the primary lobe, while the secondary and tertiary lobes have remained mostly unexplored. Previous studies have inferred that these lobes are composed of progenitors that differentiate during pupation; however, the mechanistic basis of this extended progenitor state remains unclear. This study shows that posterior lobe progenitors are maintained by a local signaling center defined by Ubx and Collier in the tertiary lobe. This Ubx zone in the tertiary lobe shares several markers with the niche of the primary lobe. Ubx domain regulates the homeostasis of the posterior lobe progenitors in normal development and an immune-challenged scenario. Our study establishes the lymph gland as a model to tease out how the progenitors interface with the dual niches within an organ during development and disorders.

Specification of the anterior hindbrain and establishment of a normal mid/hindbrain organizer is dependent on Gbx2 gene function

Development ◽  
1997 ◽  
Vol 124 (15) ◽  
pp. 2923-2934 ◽  
Author(s):  
K.M. Wassarman ◽  
M. Lewandoski ◽  
K. Campbell ◽  
A.L. Joyner ◽  
J.L. Rubenstein ◽  
...  
Keyword(s):  
Normal Development ◽  
Motor Nerve ◽  
Homeobox Gene ◽  
Neural Plate ◽  
Mouse Embryos ◽  
Loss Of Function ◽  
Isthmic Nuclei ◽  
Signaling Center ◽  
Derivatives Of ◽  
Anterior Posterior

Analysis of mouse embryos homozygous for a loss-of-function allele of Gbx2 demonstrates that this homeobox gene is required for normal development of the mid/hindbrain region. Gbx2 function appears to be necessary at the neural plate stage for the correct specification and normal proliferation or survival of anterior hindbrain precursors. It is also required to maintain normal patterns of expression at the mid/hindbrain boundary of Fgf8 and Wnt1, genes that encode signaling molecules thought to be key components of the mid/hindbrain (isthmic) organizer. In the absence of Gbx2 function, isthmic nuclei, the cerebellum, motor nerve V, and other derivatives of rhombomeres 1–3 fail to form. Additionally, the posterior midbrain in the mutant embryos appears to be extended caudally and displays abnormalities in anterior/posterior patterning. The failure of anterior hindbrain development is presumably due to the loss of Gbx2 function in the precursors of the anterior hindbrain. However, since Gbx2 expression is not detected in the midbrain it seems likely that the defects in midbrain anterior/posterior patterning result from an abnormal isthmic signaling center. These data provide genetic evidence for a link between patterning of the anterior hindbrain and the establishment of the mid/hindbrain organizer, and identify Gbx2 as a gene required for these processes to occur normally.

TrioGEF1 controls Rac- and Cdc42-dependent cell structures through the direct activation of rhoG

2000 ◽  
Vol 113 (4) ◽  
pp. 729-739 ◽  
Author(s):  
A. Blangy ◽  
E. Vignal ◽  
S. Schmidt ◽  
A. Debant ◽  
C. Gauthier-Rouviere ◽  
...  
Keyword(s):  
Rho Gtpases ◽  
Active Sites ◽  
Dominant Negative ◽  
Signaling Cascade ◽  
Microtubule Network ◽  
Cell Structures ◽  
Dependent Cell

Rho GTPases regulate the morphology of cells stimulated by extracellular ligands. Their activation is controlled by guanine exchange factors (GEF) that catalyze their binding to GTP. The multidomain Trio protein represents an emerging class of Ρ regulators that contain two GEF domains of distinct specificities. We report here the characterization of Rho signaling pathways activated by the N-terminal GEF domain of Trio (TrioD1). In fibroblasts, TrioD1 triggers the formation of particular cell structures, similar to those elicited by RhoG, a GTPase known to activate both Rac1 and Cdc42Hs. In addition, the activity of TrioD1 requires the microtubule network and relocalizes RhoG at the active sites of the plasma membrane. Using a classical in vitro exchange assay, TrioD1 displays a higher GEF activity on RhoG than on Rac1. In fibroblasts, expression of dominant negative RhoG mutants totally abolished TrioD1 signaling, whereas dominant negative Rac1 and Cdc42Hs only led to partial and complementary inhibitions. Finally, expression of a Rho Binding Domain that specifically binds RhoG(GTP) led to the complete abolition of TrioD1 signaling, which strongly supports Rac1 not being activated by TrioD1 in vivo. These data demonstrate that Trio controls a signaling cascade that activates RhoG, which in turn activates Rac1 and Cdc42Hs.

scholarly journals Characterization of an archaeal family 4 uracil DNA glycosylase and its interaction with PCNA and chromatin proteins

2005 ◽  
Vol 387 (3) ◽  
pp. 859-863 ◽  
Author(s):  
Isabelle DIONNE ◽  
Stephen D. BELL
Keyword(s):  
Protein S ◽  
Dna Glycosylase ◽  
Nuclear Antigen ◽  
Uracil Dna Glycosylase ◽  
Sliding Clamp ◽  
C Terminus ◽  
Marked Preference ◽  
Chromatin Proteins ◽  
Mechanistic Basis

We describe the characterization of a family 4 UDG1 (uracil DNA glycosylase) from the crenarchaeote Sulfolobus solfataricus. UDG1 is found to have a marked preference for substrates containing a G:U base pair over either A:U or single-stranded uracil-containing DNA substrates. UDG1 is found to interact with the sliding clamp PCNA (proliferating cell nuclear antigen), and does so by a conserved motif in the C-terminus of the protein. S. solfataricus has a heterotrimeric PCNA, and only one of the subunits, PCNA3, interacts with UDG1. We have been unable to detect any stimulation of UDG activity by PCNA, in contrast with the observed effects of PCNA on a number of DNA metabolic enzymes. However, analysis of the effects of Sulfolobus chromatin proteins on UDG1 leads us to propose a mechanistic basis for coupling UDG1 to the replication fork.

scholarly journals Structural and Compositional Characterization of Suppression of Uniform Ripening in Grapevine: A Paradoxical Ripening Disorder of Grape Berries with No Known Causative Clues

2014 ◽  
Vol 139 (5) ◽  
pp. 567-581 ◽  
Author(s):  
Bhaskar Bondada
Keyword(s):  
Titratable Acidity ◽  
Fleshy Fruit ◽  
Grape Berries ◽  
Tissue Organization ◽  
Tartaric Acids ◽  
Sieve Tubes ◽  
Mechanistic Basis ◽  
Function Relationship ◽  
Microscopy Techniques

Grapes (Vitis vinifera) have been used as a model system for understanding ripening and ripening-related physiological disorders in fleshy fruit; hence, a comparative analysis was undertaken to explore the mechanistic basis of a paradoxical ripening phenomenon of grape berries known as suppression of uniform ripening (SOUR) shrivel. Fruit organoleptic attributes coupled with morphology and structure, and tissue organization in various organs of healthy and afflicted field-grown grapevines were examined using a range of microscopy techniques. As opposed to healthy berries, SOUR shrivel berries were flaccid and had the lowest pH and lowest levels of sugars, potassium (K), and malic acid that paralleled with a significant reduction in the synthesis of anthocyanin. On the other hand, titratable acidity, tartaric acids, and tannins were much higher than perfectly healthy berries. The SOUR shrivel cluster tinged its rachis red but held no relationship with flaccidity of the berries because healthy vines totally devoid of SOUR shrivel clusters also displayed same coloration. Furthermore, although the phloem sieve tubes in both cases were plugged with callose, a carbohydrate generally implicated in impeding translocation in phloem, the afflicted grapevines exhibited relatively more plugged sieve tubes. The study revealed that the spatiotemporal configuration of cell and tissue communities determining the structure–function relationship remained intact in afflicted vines throughout the growing season. However, the functionality, especially of flows in phloem sieve tubes, started to decelerate after veraison (initiation of ripening) most likely as a result of early activation of callose synthesis and subsequently plugging of sieve plates during the remaining course of ripening. Hence, in future studies, a broader analysis of phloem sieve tubes entailing its flows and ultrastructure in phloem-girdled grapevines simulating symptoms of SOUR shrivel is needed to characterize the mechanistic basis of SOUR shrivel.

scholarly journals Future Psychologist's Mental Orientation at the Correctional Support of the Children with Impaired Mental and Physical Development

2021 ◽  
Vol 12 (3) ◽  
pp. 127-148
Author(s):  
Hanna Afuzova ◽  
Liliia Rudenko ◽  
Nataliya Stepanchenko ◽  
Veronika Shkrabiuk ◽  
Oksana Martsyniak-Dorosh ◽  
...  
Keyword(s):  
Empirical Research ◽  
Normal Development ◽  
Physical Development ◽  
Professional Activity ◽  
Professional Orientation ◽  
Complicated Process ◽  
The Future ◽  
Psychological Assistance ◽  
Orientation Phenomenon

The practice of the integrated techniques of teaching children with impaired development of various nosological categories in comprehensive schools together with children with normal development is becoming increasingly extensive alongside with a series of researches in this direction. As it follows, in this complicated process a mentally correctional support of an educated specialist is essential for a child with impaired mental and physical development. The findings of the theoretical analysis of the role and place of the orientation phenomenon in the personality's professional activity have been given. Particular attention is focused upon the content, structure and formation levels of the personality's professional orientation in adolescence; as well as on the peculiarities of the correctional support in the context of the psychological assistance to the children with alternative abilities. The specificity of the empirical research of the peculiarities of future psychologists' professional orientation at the correctional support of alternatively able children has been described. The qualification characterization of a future special psychologist's support has been presented, the techniques and methods of the investigation of the psychological peculiarities of the professional orientation at correctional support have been outlined, the findings of the empirical research have been analyzed. The theoretical and methodological foundations of the psychological provision of the formation process of the future psychologist's professional orientation at the correctional support of the children with alternative abilities have been discussed. The organization of the activity aimed at the development of the future special psychologists' professional orientation has been described, methodological apparatus has been worked out and the approbation results have been adduced. On the basis of the findings the conclusion may be drawn that the suggested methodology is correct, the tasks have been successfully performed, the objective has been achieved, the efficiency of the methodological recommendations has been verified.

Characterization of the genetics of mucosal melanoma in patients treated with immunotherapy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9556-9556
Author(s):  
Elizabeth Iannotti Buchbinder ◽  
Jason L. Weirather ◽  
Michael P. Manos ◽  
Ryan C. Brennick ◽  
Patrick Alexander Ott ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
High Response Rate ◽  
Mucosal Melanoma ◽  
Rare Type ◽  
Kit Mutation ◽  
Mutational Burden ◽  
Tumor Mutational Burden ◽  
Melanoma Patients ◽  
Mechanistic Basis

9556 Background: Mucosal melanomas can be effectively treated with checkpoint inhibitors, although the response rates are lower than those observed for melanomas arising in cutaneous sites. The mechanistic basis for the lower efficacy of immunotherapies in mucosal melanoma has been suggested to be related to their lower mutational burden. However, there has been limited characterization of the genetics in this melanoma subtype. Methods: Tumor genotyping was performed on all mucosal melanoma patients seen within the Dana Farber Cancer Institute from 2011 until the present by Oncopanel analysis. Results: We identified a total of 57 mucosal melanoma patients whose tumors had been genotyped. Of these 42 received immunotherapy and had response data available. Within the cohort of mucosal melanoma patients, 37.3% had durable clinical benefit (DCB) to their first line of IO therapy. These patients had an average mutational burden/megabase of 6.41 (95% CI 3.53-11.01) but tumor mutational burden did not correlate with response in this cohort. The pattern of mutations in mucosal melanomas was distinct from cutaneous melanomas, as the most frequent mutations were in SF3B1, ATRX, KIT and NF1 genes. Patients with KIT aberrations had a higher DCB rate compared patients with wildtype KIT (73 vs. 33%). In addition, there were several genetic differences observed based upon the site of origin of the mucosal melanoma. A higher rate of SF3B1 mutations was observed in patients with melanoma of anal/rectal origin while patients with vulvar/vaginal melanoma had higher rates of ATRX mutations, which frequently correlated with p53 ( TP53) mutations. Conclusions: This analysis is one of the first to look at genetic patterns in a large cohort of a relatively rare type of melanoma and correlate with response. Our findings confirm the low mutational burden observed in mucosal melanoma despite the high response rate observed in these patients. In addition, this study uncovered a higher rate of response to immunotherapy in mucosal melanoma patients with a KIT mutation.

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