Transient transcriptional silencing alters the cell cycle to promote germline stem cell differentiation in Drosophila

Transcriptional silencing is a conserved process used by embryonic germ cells to repress somatic fate and maintain totipotency and immortality. In Drosophila, this transcriptional silencing is mediated by polar granule component (pgc). Here, we show that in the adult ovary, pgc is required for timely germline stem cell (GSC) differentiation. Pgc is expressed transiently in the immediate GSC daughter (pre-cystoblast), where it mediates a pulse of transcriptional silencing. This transcriptional silencing mediated by pgc indirectly promotes the accumulation of Cyclin B (CycB) and cell cycle progression into late-G2 phase, when the differentiation factor bag of marbles (bam) is expressed. Pgc mediated accumulation of CycB is also required for heterochromatin deposition, which protects the germ line genome against selfish DNA elements. Our results suggest that transient transcriptional silencing in the pre-cystoblast re-programs it away from self-renewal and toward the gamete differentiation program

Temporal and Spatial Control of Germ-Plasm RNAs

SummaryIn many species, germ cells form in a specialized germ plasm, which contains localized maternal RNAs [1–5]. In the absence of active transcription in early germ cells, these maternal RNAs encode germ-cell components with critical functions in germ-cell specification, migration, and development [6, 7]. For several RNAs, localization has been correlated with release from translational repression, suggesting an important regulatory function linked to localization [3, 4, 8, 9]. To address the role of RNA localization and translational control more systematically, we assembled a comprehensive set of RNAs that are localized to polar granules, the characteristic germ-plasm organelles. We find that the 3′-untranslated regions (UTRs) of all RNAs tested control RNA localization and instruct distinct temporal patterns of translation of the localized RNAs. We demonstrate necessity for translational timing by swapping the 3′UTR of polar granule component (pgc), which controls translation in germ cells, with that of nanos, which is translated earlier. Translational activation of pgc is concurrent with extension of its poly(A) tail length but appears largely independent of the Drosophila CPEB homolog ORB. Our results demonstrate a role for 3′UTR mediated translational regulation in fine-tuning the temporal expression of localized RNA, and this may provide a paradigm for other RNAs that are found enriched at distinct cellular locations such as the leading edge of fibroblasts or the neuronal synapse

A comparative evaluation : oral leukoplakia surgical management using diode laser, CO2 laser, and cryosurgery

The comparatively evaluate the three surgical treatment modalities namely cryosurgery, diode and CO2 laser surgery in terms of healing outcomes on the day of surgery, first and second week post operatively and recurrence at the end of 18 months was assessed. Thirty selected patients were divided randomly into three groups. Each group comprising of ten patients were subjected to one of the three modalities of treatment namely cryosurgery, diode laser or CO2 laser surgery for ablation of OL. Obtained data was analyzed using mainly using Chi-square and Anova tests. Study showed statistical significant differences (p > 0.05) for evaluation parameters like pain, edema and scar. The parameters like infection, recurrence, bleeding showed no statistical significance. Pain was significantly higher in CO2 laser surgery group as compared with diode laser group. There was no recurrence observed at the end of the 6 months follow up period in all the three study groups. Observations from the study highlights that all three surgical modalities used in this study were effective for treatment of OL, and the overall summation of the results of the study showed that laser therapy (CO2 and Diode) seems to offer better clinically significant results than cryotherapy

Distributed Uplink Power Control for Optimal SIR Assignment in Cellular Data Networks

Abstract—The classical power control algorithms in wireless cellular networks have found wide applicability in attaining fixed SIR targets. This paper presents a distributed mechanism to jointly optimize SIR assignment and transmitted power in a multicellular network. Not all SIR assignments are feasible due to interference between mobile stations. We provide a new characterization of the feasible SIR region in terms of the loads on the base stations and an indication of the potential interference from mobile stations which we term spillage. Based on this characterization, we first develop a distributed algorithm that can achieve any Paretooptimal SIR assignment. Next, we pose the problem of maximizing a network-wide criterion as a utility maximization problem and present an algorithm that distributively optimizes the SIR assignment over the Pareto-optimal points. We overcome the bottleneck of centralized computation typically required for such an optimization of a network utility by exploiting the new load-spillage characterization. Extensions to power-constrained and interferenceconstrained cases are carried out. Convergence and optimality proofs as well as simulation examples using 3GPP uplink evaluation tools are presented. I

Distributed Uplink Power Control for Optimal SIR Assignment in Cellular Data Networks

Abstract—This paper solves the joint power control and SIR assignment problem through distributed algorithms in the uplink of multi-cellular wireless networks. The 1993 Foschini-Miljanic distributed power control can attain a given fixed and feasible SIR target. In data networks, however, SIR needs to be jointly optimized with transmit powers in wireless data networks. In the vast research literature since the mid-1990s, solutions to this joint optimization problem are either distributed but suboptimal, or optimal but centralized. For convex formulations of this problem, we report a distributed and optimal algorithm. The main issue that has been the research bottleneck is the complicated, coupled constraint set, and we resolve it through a reparametrization via the left Perron Frobenius eigenvectors, followed by development of a locally computable ascent direction. A key step is a new characterization of the feasible SIR region in terms of the loads on the base stations, and an indication of the potential interference from mobile stations, which we term spillage. Based on this load-spillage characterization, we first develop a distributed algorithm that can achieve any Pareto-optimal SIR assignment, then a distributed algorithm that picks out a particular Pareto-optimal SIR assignment and the associated powers through utility maximization. Extensions to power-constrained and interference-constrained cases are carried out. The algorithms are theoretically sound and practically implementable: we present convergence and optimality proofs as well as simulations using 3GPP network and path loss models. I

Network Pricing and Rate Allocation with Content Provider Participation

Abstract—Pricing content-providers for connectivity to endusers and setting connection parameters based on the price is an evolving model on the Internet. The implications are heavily debated in telecom policy circles, and some advocates of “Network Neutrality ” have opposed price based differentiation in connectivity. However, pricing content providers can possibly subsidize the end-user’s cost of connectivity, and the consequent increase in end-user demand can benefit ISPs and content providers. This paper provides a framework to quantify the precise trade-off in the distribution of benefits among ISPs, content-providers, and end-users. The framework generalizes the well-known utility maximization based rate allocation model, which has been extensively studied as an interplay between the ISP and the end-users, to incorporate pricing of content-providers. We derive the resulting equilibrium prices and data rates in two different ISP market conditions: competition and monopoly. Network neutrality based restriction on content-provider pricing is then modeled as a constraint on the maximum price that can be charged to content-providers. We demonstrate that, in addition to gains in total and enduser surplus, content-provider experiences a net surplus from participation in rate allocation under low cost of connectivity. The surplus gains are, however, limited under monopoly conditions in comparison to competition in the ISP market

A switch in the mode of Wnt signaling orchestrates the formation of germline stem cell differentiation niche in Drosophila.

Germline stem cell (GSC) self-renewal and differentiation into gametes is regulated by both intrinsic factors in the germ line as well as extrinsic factors from the surrounding somatic niche. dWnt4, in the escort cells of the adult somatic niche promotes GSC differentiation using the canonical β-catenin-dependent transcriptional pathway to regulate escort cell survival, adhesion to the germ line and downregulation of self-renewal signaling. Here, we show that in addition to the β-catenin-dependent canonical pathway, dWnt4 also uses downstream components of the Wnt non-canonical pathway to promote escort cell function earlier in development. We find that the downstream non-canonical components, RhoA, Rac1 and cdc42, are expressed at high levels and are active in escort cell precursors of the female larval gonad compared to the adult somatic niche. Consistent with this expression pattern, we find that the non-canonical pathway components function in the larval stages but not in adults to regulate GSC differentiation. In the larval gonad, dWnt4, RhoA, Rac1 and cdc42 are required to promote intermingling of escort cell precursors, a function that then promotes proper escort cell function in the adults. We find that dWnt4 acts by modulating the activity of RhoA, Rac1 and cdc42, but not their protein levels. Together, our results indicate that at different points of development, dWnt4 switches from using the non-canonical pathway components to using a β-catenin-dependent canonical pathway in the escort cells to facilitate the proper differentiation of GSCs

The downstream Wnt non-canonical components are required in the escort cells for proper germline stem cell differentiation.

<p>(A) Schematic of a female late larval gonad. The primordial germ cells (PGCs) (blue) are interspersed with the intermingled cells (ICs) (red), precursors of escort cells. (B) A schematic of the <i>Drosophila</i> female germarium present at the anterior end of the ovarioles. The germ line consists of germline stem cells (GSCs) (blue) that are attached to the self-renewal somatic niche made by the terminal filament and cap cells (orange). The GSCs divide to give rise to the cystoblast (blue) that differentiates on expression of a differentiating factor, Bam. The differentiating cystoblast (green) undergoes four incomplete mitotic divisions (green) to give rise to a sixteen-cell cyst (green), one of which becomes an oocyte (grey). The differentiating somatic niche made by the escort cells (red) encapsulates the cystoblast and the differentiating progeny. C) An illustration of the dWnt non-canonical pathway. dWnt binds to its receptor, Frizzled/Frizzled2 (Fz/Fz2) and activates DAAM1, RhoA, Rac1, and cdc42, downstream of Dsh. RhoA activates ROCK. These pathways are required for actin remodeling, cell movement and cell polarity. (D-I) Germaria of <i>c587-GAL4</i> (control) and <i>dsh</i>, <i>DAAM1</i>, <i>RhoA</i>, <i>Rac1</i> and <i>cdc42</i> depleted escort cells stained with 1B1 (red) and Vasa (blue) showing an accumulation of >3 undifferentiated cells in <i>dsh</i>, <i>DAAM1</i>, <i>RhoA</i>, <i>Rac1</i> and <i>cdc42</i> mutants (yellow line). (J) Percentage of the germaria with >3 spectrosomes in <i>c587-GAL4</i>, <i>dsh</i>, <i>DAAM1</i>, <i>RhoA</i>, <i>Rac1</i> and <i>cdc42</i> depleted escort cells showing a significant difference in mutants (n = 50). (K-P) <i>dWnt4</i> heterozygote; <i>dWnt4</i>/<i>dsh</i>^<i>1</i>; <i>dWnt4</i>/<i>DAAM</i>; <i>dWnt4</i>,<i>RhoA</i>; <i>dWnt4</i>/<i>Rac1</i> and <i>dWnt4</i>/<i>cdc42</i>^<i>3</i> trans-heterozygote stained with 1B1 (red) and Vasa (blue) showing an accumulation of >3 undifferentiated cells (yellow line) in the trans-heterozygotes. (Q) Percentage of the differentiation defects in <i>dWnt4</i> heterozygote, <i>dWnt4</i>/<i>dsh</i>^<i>1</i>; <i>dWnt4</i>/<i>DAAM</i>; <i>dWnt4</i>,<i>RhoA</i>; <i>dWnt4</i>/<i>Rac1</i> and <i>dWnt4</i>/<i>cdc42</i>^<i>3</i> trans-heterozygote showing a significant difference in trans-heterozygotes (n = 50). Scale bar for all images is 20μm.</p