scholarly journals Expression of human HIPKs in Drosophila demonstrates their shared and unique functions in a developmental model

2021 ◽  
Author(s):  
Stephen D Kinsey ◽  
Justin P Vinluan ◽  
Gerald A Shipman ◽  
Esther M Verheyen
Keyword(s):  
Morphological Changes ◽  
Fruit Fly ◽  
Developmental Model ◽  
Developmental Pathways ◽  
Morphological Development ◽  
Vertebrate Development ◽  
Genetic Redundancy ◽  
Interacting Protein ◽  
Developmental Context ◽  
Insight Into

Abstract Homeodomain-interacting protein kinases (HIPKs) are a family of four conserved proteins essential for vertebrate development, as demonstrated by defects in the eye, brain, and skeleton that culminate in embryonic lethality when multiple HIPKs are lost in mice. While HIPKs are essential for development, functional redundancy between the four vertebrate HIPK paralogues has made it difficult to compare their respective functions. Because understanding the unique and shared functions of these essential proteins could directly benefit the fields of biology and medicine, we addressed the gap in knowledge of the four vertebrate HIPK paralogues by studying them in the fruit fly Drosophila melanogaster, where reduced genetic redundancy simplifies our functional assessment. The single hipk present in the fly allowed us to perform rescue experiments with human HIPK genes that provide new insight into their individual functions not easily assessed in vertebrate models. Further, the abundance of genetic tools and established methods for monitoring specific developmental pathways and gross morphological changes in the fly allowed for functional comparisons in endogenous contexts. We first performed rescue experiments to demonstrate the extent to which each of the human HIPKs can functionally replace Drosophila Hipk for survival and morphological development. We then showed the ability of each human HIPK to modulate Armadillo/β-catenin levels, JAK/STAT activity, proliferation, growth, and death, each of which have previously been described for Hipks, but never all together in comparable tissue contexts. Finally, we characterized novel developmental phenotypes induced by human HIPKs to gain insight to their unique functions. Together, these experiments provide the first direct comparison of all four vertebrate HIPKs to determine their roles in a developmental context.

scholarly journals Functional characterization of human Homeodomain-interacting protein kinases (HIPKs) in Drosophila melanogaster reveal both conserved functions and differential induction of HOX gene expression

2020 ◽  
Author(s):  
Stephen D. Kinsey ◽  
Gerald A. Shipman ◽  
Esther M. Verheyen
Keyword(s):  
Gene Expression ◽  
Drosophila Melanogaster ◽  
Protein Kinases ◽  
Functional Characterization ◽  
Fruit Fly ◽  
Polycomb Group ◽  
Genetic Redundancy ◽  
Interacting Protein ◽  
Developmental Potential ◽  
Hox Gene

AbstractHomeodomain-interacting protein kinases (Hipks) are a family of conserved proteins that are necessary for development in both invertebrate and vertebrate organisms. Vertebrates have four paralogues, Hipks 1-4. Mice lacking Hipk1 or Hipk2 are viable, however loss of both is lethal during early embryonic development, with embryos exhibiting homeotic skeletal transformations and incorrect HOX gene expression. While these results suggest Hipks have a role in regulating HOX genes, a regulatory mechanism has not been characterized, and further comparisons of the roles of Hipks in development has not progressed. One challenge with characterizing developmental regulators in vertebrates is the extensive redundancy of genes. For this reason, we used Drosophila melanogaster, which has reduced genetic redundancy, to study the functions of the four human HIPKs (hHIPKs). In D. melanogaster, zygotic loss of the single ortholog dhipk results in lethality with distinct eye and head defects. We used a dhipk mutant background to compare the ability of each hHIPK protein to rescue the phenotypes caused by the loss of dHipk. In these humanized flies, both hHIPK1 and hHIPK2 rescued lethality, while hHIPK3 and hHIPK4 only rescued minor dhipk mutant patterning phenotypes. This evidence for conserved functions of hHIPKs in D. melanogaster directed our efforts to identify and compare the developmental potential of hHIPKs by expressing them in well-defined tissue domains and monitoring changes in phenotypes. We observed unique patterns of homeotic transformations in flies expressing hHIPK1, hHIPK2, or hHIPK3 caused by ectopic induction of Hox proteins. These results were indicative of inhibited Polycomb-group complex (PcG) components, suggesting that hHIPKs play a role in regulating its activity. Furthermore, knockdown of PcG components phenocopied hHIPK and dHipk expression phenotypes. Together, this data shows that hHIPKs function in D. melanogaster, where they appear to have variable ability to inhibit PcG, which may reflect their roles in development.Author summaryThe redundancy of vertebrate genes often makes identifying their functions difficult, and Hipks are no exception. Individually, each of the four vertebrate Hipks are expendable for development, but together they are essential. The reason Hipks are necessary for development is unclear and comparing their developmental functions in a vertebrate model is difficult. However, the invertebrate fruit fly has a single essential dhipk gene that can be effectively removed and replaced with the individual vertebrate orthologs. We used this technique in the fruit fly to compare the developmental capacity of the four human HIPKs (hHIPKs). We found that hHIPK1 and hHIPK2 are each able to rescue the lethality caused by loss of dhipk, while hHIPK3 and hHIPK4 rescue minor patterning defects, but not lethality. We then leveraged the extensive adult phenotypes associated with genetic mutants in the fruit fly to detect altered developmental pathways when hHIPKs are mis-expressed. We found that expression of hHIPKs 1-3 or dhipk each produce phenotypes that mimic loss of function of components of the Polycomb-group complex, which are needed to regulate expression of key developmental transcription factors. We therefore propose that Hipks inhibit Polycomb components in normal development, though details of this interaction remain uncharacterized.

An atomic-level insight into the basic mechanism responsible for the enhancement of the catalytic oxidation of carbon monoxide on a Cu/CeO2 surface

2017 ◽  
Vol 19 (5) ◽  
pp. 3498-3505 ◽  
Author(s):  
Kenichi Koizumi ◽  
Katsuyuki Nobusada ◽  
Mauro Boero
Keyword(s):  
Carbon Monoxide ◽  
Reaction Mechanism ◽  
Catalytic Oxidation ◽  
Morphological Changes ◽  
Basic Mechanism ◽  
Atomic Level ◽  
Insight Into ◽  
Oxidation Of Carbon Monoxide

Reaction mechanism of CO molecules onto a Cu/CeO2 surface and morphological changes.

scholarly journals Genome-Wide Identification of CBL-CIPK Gene Family in Honeysuckle (Lonicera japonica Thunb.) and Their Regulated Expression Under Salt Stress

2021 ◽  
Vol 12 ◽  
Author(s):  
Luyao Huang ◽  
Zhuangzhuang Li ◽  
Qingxia Fu ◽  
Conglian Liang ◽  
Zhenhua Liu ◽  
...  
Keyword(s):  
Salt Stress ◽  
Protein Kinases ◽  
Stress Responses ◽  
Structure Prediction ◽  
Functional Divergence ◽  
Gene Families ◽  
Plant Responses ◽  
Interacting Protein ◽  
Protein Motifs ◽  
Insight Into

In plants, calcineurin B-like proteins (CBLs) are a unique group of Ca2+ sensors that decode Ca2+ signals by activating a family of plant-specific protein kinases known as CBL-interacting protein kinases (CIPKs). CBL-CIPK gene families and their interacting complexes are involved in regulating plant responses to various environmental stimuli. To gain insight into the functional divergence of CBL-CIPK genes in honeysuckle, a total of six LjCBL and 17 LjCIPK genes were identified. The phylogenetic analysis along with the gene structure analysis divided both CBL and CBL-interacting protein kinase genes into four subgroups and validated by the distribution of conserved protein motifs. The 3-D structure prediction of proteins shown that most LjCBLs shared the same Protein Data Bank hit 1uhnA and most LjCIPKs shared the 6c9Da. Analysis of cis-acting elements and gene ontology implied that both LjCBL and LjCIPK genes could be involved in hormone signal responsiveness and stress adaptation. Protein-protein interaction prediction suggested that LjCBL4 is hypothesized to interact with LjCIPK7/9/15/16 and SOS1/NHX1. Gene expression analysis in response to salinity stress revealed that LjCBL2/4, LjCIPK1/15/17 under all treatments gradually increased over time until peak expression at 72 h. These results demonstrated the conservation of salt overly sensitive pathway genes in honeysuckle and a model of Ca2+-LjCBL4/LjSOS3-LjCIPK16/LjSOS2 module-mediated salt stress signaling in honeysuckle is proposed. This study provides insight into the characteristics of the CBL-CIPK gene families involved in honeysuckle salt stress responses, which could serve as a foundation for gene transformation technology, to obtain highly salt-tolerant medicinal plants in the context of the global reduction of cultivated land.

Dynamics and 2D temperature distribution of plasma obtained by femtosecond laser-induced breakdown

2021 ◽  
Author(s):  
Afaque M. Hossain ◽  
Martin Ehrhardt ◽  
Martin Rudolph ◽  
Dmitry V Kalanov ◽  
Pierre Lorenz ◽  
...  
Keyword(s):  
Femtosecond Laser ◽  
Morphological Changes ◽  
Exponential Dependence ◽  
Morphological Development ◽  
Initial State ◽  
Toroidal Plasma ◽  
Velocity Gradients ◽  
Baroclinic Torque ◽  
Laser Induced Breakdown ◽  
High Pressure Zone

Abstract Recently, plasma produced by focusing femtosecond laser in gases has been introduced as an etching tool in materials processing. Proper control of the plasma in this application necessitates the apt understanding of the different morphological features of the plasma. In this contribution we show that, the plasma produced in air goes through several stages of morphological development – from ellipsoidal to spherical to toroidal plasma, whereas in argon, axial compression of an ellipsoidal plasma is observed. To explain this dissimilarity, we have quantified the temperature by emission spectroscopy (Planck analysis with Wien’s approximation). The evolution of temperature shows a triple exponential dependence in time which can be correlated with different stages of morphological changes of the plasma. Open Source Field Operation and Manipulation (OpenFOAM) simulations using experimentally determined temperature values show that – (i) the reverse pressure gradient propagates radially inwards and compresses the plasma in both air and argon and forms a localized high pressure zone at the center that generates a secondary pressure wave in air, but not in argon, and (ii) the baroclinic torque that is generated because of the Richtmyer-Meshkov instability, dominates the rate of vorticity in air, whereas effects of flow compressibility and velocity gradients dominate the vortices in argon. Knowledge of the initial state and the dynamics of the subsequent stages of the plasma formation can be utilized for control and optimization of laser-induced plasma applications.

scholarly journals GENE-45. DISSECTING THE DRIVERS OF ADULT H3K27M-GLIOMAS AT THE SINGLE-CELL LEVEL

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi107-vi107
Author(s):  
Ilon Liu ◽  
Byron Avihai ◽  
Johannes Gojo ◽  
Keith Ligon ◽  
Thomas Czech ◽  
...  
Keyword(s):  
Single Cell ◽  
Time Window ◽  
Molecular Entity ◽  
Single Cell Level ◽  
Cell Level ◽  
Developmental Context ◽  
Level Data ◽  
Cellular Context ◽  
Insight Into ◽  
Shared Gene

Abstract Diffuse midline gliomas are characterized by a lysine27-to-methionine mutation in histone H3 (H3K27M-glioma) and represent a highly aggressive molecular entity of high-grade gliomas. These mutations have primarily been described in children, but are also increasingly recognized in adults. In pediatric H3K27M-gliomas, the transcriptional architecture and cellular composition have been studied at the single-cell level. Data suggest that these tumors arise through malignant transformation of a glial progenitor during a specific neurodevelopmental time window. On the other hand, little is known about the architecture and cellular context of adult H3K27M-gliomas, and it remains to be elucidated whether they are driven by the same or by distinct oncogenic programs as their pediatric counterparts. Here, we utilize single-cell transcriptomics to characterize the transcriptional landscape of five H3K27M-gliomas from adult patients aged 22 to 56 years (median 33 years). We describe the specific cellular and microenvironmental architecture of the adult tumors, which comprises distinct populations of cancer and normal cells. We contrast our findings to 12 location-matched pediatric H3K27M-tumors from patients aged 2.5 to 15 years (median 8 years) to identify features related to tumorigenesis and developmental context in light of the shared hallmark H3K27M mutation. Our preliminary data indicate shared gene expression programs between adult and pediatric tumors. However, we find significant differences in the composition of the immune compartment as well as less pronounced differentiation programs in the adult tumors. Our findings provide an unprecedented insight into the composition of adult H3K27M-gliomas and advance our understanding of this molecular tumor class.

scholarly journals Study of fetal and postnatal morphological development of the brain sulci

2013 ◽  
Vol 11 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Koshiro Nishikuni ◽  
Guilherme Carvalhal Ribas
Keyword(s):  
Morphological Changes ◽  
Fetal Brain ◽  
Postnatal Period ◽  
Postnatal Life ◽  
Morphological Development ◽  
Fetal Life ◽  
Brain Hemispheres ◽  
Collateral Sulcus ◽  
Fetal Brain Development ◽  
The Brain

Object The surface of the developing fetal brain undergoes significant morphological changes during fetal growth. The purpose of this study was to evaluate the morphological development of the brain sulci from the fetal to the early postnatal period. Methods Two hundred fourteen brain hemispheres from 107 human brain specimens were examined to evaluate the timing of sulcal formation, from its appearance to its complete development. These brains were obtained from cadavers ranging in age from 12 weeks of gestation to 8 months of postnatal life. Results The order of appearance of the cerebral sulci, and the number and percentages of specimens found in this study were as follows: longitudinal cerebral fissure at 12 weeks (10/10, 100%); callosal sulcus at 12 weeks (10/10, 100%); hippocampal sulcus at 15 weeks (7/10, 70%); lateral sulcus at 17 weeks (20/22, 90.9%); circular insular sulcus at 17 weeks (18/22, 81.8%); olfactory sulcus at 17 weeks (18/22, 81.8%); calcarine sulcus at 17 weeks (14/22, 63.6%); parietooccipital sulcus at 17 weeks (11/22, 50%); cingulate sulcus at 19 weeks (16/20, 80%); central sulcus at 21 weeks (22/38, 57.9%); orbital sulcus at 22 weeks (9/16, 56.2%); lunate sulcus at 24 ± 2 weeks (12/16, 75%); collateral sulcus at 24 ± 2 weeks (8/16, 50%); superior frontal sulcus at 25 ± 2 weeks (5/6, 83.3%); rhinal sulcus at 25 ± 2 weeks (3/6, 50%); precentral sulcus at 26 ± 3 weeks (2/4, 50%); postcentral sulcus at 26 ± 3 weeks (2/4, 50%); superior temporal sulcus at 26 ± 3 weeks (2/4, 50%); central insular sulcus at 29 ± 2 weeks (4/4, 100%); intraparietal sulcus at 29 ± 2 weeks (2/4, 50%); paraolfactory sulcus at 29 ± 2 weeks (2/4, 50%); inferior frontal sulcus at 30 ± 3 weeks (2/4, 50%); transverse occipital sulcus at 30 ± 3 weeks (2/4, 50%); occipitotemporal sulcus at 30 ± 3 weeks (2/4, 50%); marginal branch of the cingulate sulcus at 30 ± 3 weeks (2/4, 50%); paracentral sulcus at 30 ± 3 weeks (2/4, 50%); subparietal sulcus at 30 ± 3 weeks (2/4, 50%); inferior temporal sulcus at 31 ± 3 weeks (3/6, 50%); transverse temporal sulcus at 33 ± 3 weeks (6/8, 75%); and secondary sulcus at 38 ± 3 weeks (2/4, 50%). Conclusions The brain is subjected to considerable morphological changes throughout gestation. During fetal brain development the cortex begins to fold in, thereby increasing the cortical surface. All primary sulci are formed during fetal life. The appearance of each sulcus follows a characteristic timing pattern, which may be used as one of the reliable guides pertinent to gestational age and normal fetal development.

Cretaceous Diatoms: Morphology, Taxonomy, Biostratigraphy

1995 ◽  
Vol 8 ◽  
pp. 81-106 ◽  
Author(s):  
David M. Harwood ◽  
Vladimir A. Nikolaev
Keyword(s):  
Lower Cretaceous ◽  
Morphological Changes ◽  
Early History ◽  
Background Information ◽  
Morphological Development ◽  
Diatom Assemblages ◽  
History Of

The Cretaceous record of the diatoms presented here outlines our understanding of their early morphological development. Recent documentation of well preserved Lower Cretaceous (Aptian/Albian) diatom assemblages provides a window into the early history of the diatoms and serves as a base for comparing their subsequent morphological changes. A brief review of diatom biology and morphology is provided to introduce this paper and that of Barron and Baldauf (this volume). Additional background information on the diatoms can be found in the works of Schrader and Schuette (1981), Tappan (1980), Bach and Burkhardt (1984), Barron (1985a, 1993), Fenner (1985), Ricard (1987), Bradbury (1988), Round et al. (1990), and Picket-Heaps et al. (1990).

scholarly journals Invertebrate models of behavioural plasticity and human disease

2018 ◽  
Vol 2 ◽  
pp. 239821281881806 ◽  
Author(s):  
Lindy Holden-Dye ◽  
Robert J. Walker
Keyword(s):  
Neuronal Excitability ◽  
Fruit Fly ◽  
Mammalian Brain ◽  
Behavioural Plasticity ◽  
Molecular Architecture ◽  
Neural Communication ◽  
Systems Learning ◽  
Invertebrate Animals ◽  
Invertebrate Models ◽  
Insight Into

The fundamental processes of neural communication have been largely conserved through evolution. Throughout the last century, researchers have taken advantage of this, and the experimental tractability of invertebrate animals, to advance understanding of the nervous system that translates to mammalian brain. This started with the inspired analysis of the ionic basis of neuronal excitability and neurotransmission using squid during the 1940s and 1950s and has progressed to detailed insight into the molecular architecture of the synapse facilitated by the genetic tractability of the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster. Throughout this time, invertebrate preparations have provided a means to link neural mechanisms to behavioural plasticity and thus key insight into fundamental aspects of control systems, learning, and memory. This article captures key highlights that exemplify the historical and continuing invertebrate contribution to neuroscience.

Autophagy is involved in starvation response and cell death in Blastocystis

Microbiology ◽  
2010 ◽  
Vol 156 (3) ◽  
pp. 665-677 ◽  
Author(s):  
Jing Yin ◽  
Angeline J. J. Ye ◽  
Kevin S. W. Tan
Keyword(s):  
Cell Death ◽  
Amino Acid ◽  
Morphological Changes ◽  
Central Vacuole ◽  
Starvation Response ◽  
The Core ◽  
Large Size ◽  
Transmission Electron ◽  
Membrane Bound ◽  
Insight Into

Previous studies have demonstrated that colony forms of Blastocystis undergo cell death with numerous membrane-bound vesicles containing organelles located within the central vacuole, resembling morphological features of autophagy. In this study, we investigated whether Blastocystis underwent autophagy upon amino acid starvation and rapamycin treatment. Concurrently, we provide new insight into a possible function of the central vacuole. The use of the autophagy marker monodansylcadaverine, and the autophagy inhibitors3-methyladenine and wortmannin, showed the existence of autophagy in amino-acid-starved and rapamycin-treated Blastocystis. Confocal microscopy and transmission electron microscopy studies also showed morphological changes that were suggestive of autophagy. The unusually large size of the autophagic compartments within the parasite central vacuole was found to be unique in Blastocystis. In addition, autophagy was found to be triggered when cells were exposed to the cytotoxic antibody mAb 1D5, and autophagy was intensified in the presence of the caspase inhibitor zVAD.fmk. Taken together, our results suggest that the core machinery for autophagy is conserved in Blastocystis, and that it plays an important role in the starvation response and cell death of the parasite.

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