Ankita Singh

Regulation of Notch Signaling by the Heterogeneous Nuclear Ribonucleoprotein Hrp48 and Deltex in Drosophila melanogaster

Notch signaling is an evolutionarily conserved pathway that is found to be involved in a number of cellular events throughout development. The deployment of the Notch signaling pathway in numerous cellular contexts is possible due to its regulation at multiple levels. In an effort to identify the novel components integrated into the molecular circuitry affecting Notch signaling, we carried out a protein–protein interaction screen based on the identification of cellular protein complexes using co-immunoprecipitation followed by mass-spectrometry. We identified Hrp48, a heterogeneous nuclear ribonucleoprotein in Drosophila, as a novel interacting partner of Deltex (Dx), a cytoplasmic modulator of Notch signaling. Immunocytochemical analysis revealed that Dx and Hrp48 colocalize in cytoplasmic vesicles. The dx mutant also showed strong genetic interactions with hrp48 mutant alleles. The coexpression of Dx and Hrp48 resulted in the depletion of cytoplasmic Notch in larval wing imaginal discs and downregulation of Notch targets cut and wingless. Previously, it has been shown that Sex-lethal (Sxl), on binding with Notch mRNA, negatively regulates Notch signaling. The overexpression of Hrp48 was found to inhibit Sxl expression and consequently rescued Notch signaling activity. In the present study, we observed that Dx together with Hrp48 can regulate Notch signaling in an Sxl-independent manner. In addition, Dx and Hrp48 displayed a synergistic effect on caspase-mediated cell death. Our results suggest that Dx and Hrp48 together negatively regulate Notch signaling in Drosophila melanogaster.

Van der Woude Syndrome Associated with Hypodontia: A Rare Clinical Entity

Van der Woude syndrome (VWS) is usually underreported and frequently not diagnosed. The phenomenon that cleft lip and palate are regularly combined in the same pedigree makes it unique. A meticulous examination of a patient with lip pits may reveal a hidden form of a cleft, for example, submucous. This paper presents a case of VWS in a ten-year-old boy with characteristic orofacial features. Special emphasis has also been given on the need for appropriate genetic counseling.

Deltex interacts with Eiger and consequently influences the cell death in Drosophila melanogaster

TNF-JNK signaling is one of the highly conserved signaling pathways that regulate a broad spectrum of cellular processes including proliferation and apoptosis. Eiger, the sole homologue of TNF in Drosophila, initiates the TNF-JNK pathway to induce cell death. Previously, Deltex (Dx) has been identified as a Notch signaling component that regulates vesicular trafficking of Notch. In the present study, we have investigated the interaction between these two proteins in order to identify how Dx influences the activity of Eiger. Dx is found to act as a novel modulator of JNK-mediated cell death inducing activity of Eiger. Additionally, we observe that dx genetically interacts with eiger during wing development, and these two proteins, Dx and Eiger, colocalize in the cytoplasm. Our analysis reveals that Dx is involved in the cytoplasmic relocalization of Eiger from the cell membrane, thereby influencing Eiger-mediated JNK-activation process. Moreover, we demonstrate that Dx potentiates the activity of Eiger to downregulate Notch signaling pathway by retaining the Notch protein in the cytoplasm. Together, our findings reveal a novel role of Dx to modulate the signaling activity of Eiger and subsequent JNK-mediated cell death.

SEM Analysis and Management of Fracture Dental Implant

Implant fracture is one of the important biomechanical complications which can present with a considerable problem to the patient as well as the dental surgeon. The aim of this case report is to describe the management of a case of fractured endosseous dental implant in premolar region and microscopic evaluation of the fractured implant segment using scanning electron microscopy. In most of such cases, complete removal of the fractured implant has been a preferred treatment option. In the present case, fractured implant segment was successfully removed and rehabilitated immediately with larger diameter implant. It was found that retrieved fracture segment had a diameter of 3.3 mm, and SEM analysis shows fatigue fractures which may be the result of excessive overloading and use of small diameter implant which enhances fatigue failure.

Drainage network characteristics of the Ghaghghar River Basin (GRB), Son Valley, India

ABSTRACT The present study helps to understand the relation between the different morphometric parameters to delineate the drainage characteristics of the Ghaghghar River Basin (GRB), Son Valley, India. Shuttle Radar Topographic Mission (SRTM) data were used to prepare the Digital Elevation Model (DEM), Aspect, Drainage, and Slope maps by using ArcGIS 10 software. The Ghaghghar River is third-order stream that exhibits dendritic to sub-dendritic pattern. The trails drainage patterns are also observed in some areas of the basin which may be due to the effect of regional tectonics. The mean bifurcation ratio is 5.1 showing normal basin which is somehow controlled by structural disturbances. High bifurcation ratio (>10) determines that the region is subjected to strong structural control on the drainage. Drainage density (0.36) shows very coarse drainage texture also having positive correlation with stream frequency. The elongation ratio is 0.64 along with circulatory ratio (0.6) shows elongated nature of the basin. The low values of drainage density and stream frequency imply that surface run-off is not quickly removed from the basin, making it susceptible to flooding and gully have very little effect on the extent to which the surface has been lowered by agents of denudation.

Regulation of Notch signaling in the developing Drosophila eye by a T-box containing transcription factor, Dorsocross

Owing to a multitude of functions, there is barely a tissue or a cellular process that is not being regulated by Notch signaling. To allow the Notch signal to be deployed in numerous contexts, many different mechanisms have evolved to regulate the level, duration and spatial distribution of Notch activity. To identify novel effectors of Notch signaling in Drosophila melanogaster, we analyzed the whole transcriptome of the wing and eye imaginal discs in which an activated form of Notch was overexpressed. Selected candidate genes from the transcriptome analysis were subjected to genetic interaction experiments with Notch pathway components. Among the candidate genes, T‐box encoding gene, Dorsocross (Doc) showed strong genetic interaction with Notch ligand, Delta. Genetic interaction between them resulted in reduction of eye size, loss of cone cells, and cell death, which represent prominent Notch loss of function phenotypes. Immunocytochemical analysis in Df(3L)DocA/Dl 5f trans‐heterozygous eye discs showed accumulation of Notch at the membrane. This accumulation led to decreased Notch signaling activity as we found downregulation of Atonal, a Notch target and reduction in the rate of Notch‐mediated cell proliferation. Doc mutant clones generated by FLP‐FRT system showed depletion in the expression of Delta and subsequent reduction in the Notch signaling activity. Similarly, Doc overexpression in the eye discs led to modification of Delta expression, loss of Atonal expression and absence of eye structure in pharate adults. Taken together, our results suggest that Doc regulates the expression of Delta and influence the outcome of Notch signaling in the eye discs.

Pleiotropic Functions of the Chromodomain-Containing Protein Hat-trick During Oogenesis in Drosophila melanogaster

Chromatin-remodeling proteins have a profound role in the transcriptional regulation of gene expression during development. Here, we have shown that the chromodomain-containing protein Hat-trick is predominantly expressed within the oocyte nucleus, specifically within the heterochromatinized karyosome, and that a mild expression is observed in follicle cells. Colocalization of Hat-trick with Heterochromatin Protein 1 and synaptonemal complex component C(3)G along with the diffused karyosome after hat-trick downregulation shows the role of this protein in heterochromatin clustering and karyosome maintenance. Germline mosaic analysis reveals that hat-trick is required for maintaining the dorso-ventral patterning of eggs by regulating the expression of Gurken. The increased incidence of double-strand breaks (DSBs), delayed DSB repair, defects in karyosome formation, altered Vasa mobility, and, consequently, misexpression and altered localization of Gurken in hat-trick mutant egg chambers clearly suggest a putative involvement of Hat-trick in the early stages of oogenesis. In addition, based on phenotypic observations in hat-trick mutant egg chambers, we speculate a substantial role of hat-trick in cystoblast proliferation, oocyte determination, nurse cell endoreplication, germ cell positioning, cyst encapsulation, and nurse cell migration. Our results demonstrate that hat-trick has profound pleiotropic functions during oogenesis in Drosophila melanogaster.

Notch signals modulate lgl mediated tumorigenesis by the activation of JNK signaling

ObjectivesOncogenic potential of Notch signaling and its cooperation with other factors to affect proliferation are widely established. Notch exhibits a cooperative effect with loss of a cell polarity gene, scribble to induce neoplastic overgrowth. Oncogenic Ras also show cooperative effect with loss of cell polarity genes such as scribble (scrib), lethal giant larvae (lgl) and discs large to induce neoplastic overgrowth and invasion. Our study aims at assessing the cooperation of activated Notch with loss of function of lgl in tumor overgrowth, and the mode of JNK signaling activation in this context.ResultsIn the present study, we use Drosophila as an in vivo model to show the synergy between activated Notch (Nact) and loss of function of lgl (lgl-IR) in tumor progression. Coexpression of Nact and lgl-IR results in massive tumor overgrowth and displays hallmarks of cancer, such as MMP1 upregulation and loss of epithelial integrity. We further show activation of JNK signaling and upregulation of its receptor, Grindelwald in Nact/lgl-IR tumor. In contrast to previously described Notchact/scrib−/− tumor, our experiments in Nact/lgl-IR tumor showed the presence of dying cells along with tumorous overgrowth.

Immediate implant placement in mandibular anterior region with dehiscence

Restoration of teeth in the esthetic zone is a great challenge for dental practitioners. Preference to shortened overall treatment period and minimum number of surgical interventions in implant dentistry is desired by patients and clinicians. Immediate implant placement combined with simultaneously guided bone regeneration in post extraction sockets having bony defects has emerged as a predictable method resulting in high implant survival rates and good esthetic outcomes. This article describes a case of immediate implant placement and guided bone regeneration for treatment of severe buccal dehiscence in mandibular anterior region.

Prosthetic Management of Post Surgical Nasal Skin Graft Contracture

The sequelae of trauma to the nose include nasal deformity and nasal obstruction that can have a long term negative impact on patient’s quality of life. Successful management of posttraumatic nasal obstruction relies on a detailed history, careful analysis, and accurate diagnosis. Treatment must balance the seemingly disparate goals of re-establishing structure, improving contour and esthetics, as well as restoring the nasal airway. Indications and technical steps for fabricating bilateral nasal stents are presented, for a case of surgical opening of bilateral nasal synechia necessitated due to failed initial corrective surgery, post contracture and collapse of skin grafts. The objective of nasal stent was to maintain patency of nasal passage post surgical intervention. This is achieved by support to graft and residual tissues and prevention of mouth breathing. The nasal stents were modified post insertion at regular intervals to ensure adaptation to changes in mucosal lining of nasal.