Search

Signaling pathways activated by secreted Wnt ligands play an essential role in tissue development and the progression of diseases, like cancer. Secretion of the lipid‐modified Wnt proteins is tightly regulated by a repertoire of intracellular factors. For instance, a membrane protein, Evi, interacts with the Wnt ligand in the ER, and it is essential for its further trafficking and release in the extracellular space. After dissociating from the Wnt, the Wnt‐unbound Evi is recycled back to the ER via Golgi. However, where in this trafficking path Wnt proteins dissociate from Evi remains unclear. Here, we have used the Drosophila wing epithelium to trace the route of the Evi‐Wg (Wnt homolog) complex leading up to their separation. In these polarized cells, Wg is first trafficked to the apical surface; however, the secretion of Wg is believed to occurs post‐internalization via recycling. Our results show that the Evi‐Wg complex is internalized from the apical surface and transported to the retromer‐positive endosomes. Furthermore, using antibodies that specifically label the Wnt‐unbound Evi, we show that Evi and Wg separation occurs post‐internalization in the acidic endosomes. These results refine our understanding of the polarized trafficking of Wg and highlight the importance of Wg endocytosis in its secondary secretion. [ABSTRACT FROM AUTHOR]

Glypicans are closely associated with organ development and tumorigenesis in animals. Dally-like (Dlp), a membrane-bound glypican, plays pivotal roles in various biological processes in Drosophila. In this study, we observed that an excess of Dlp led to the malformation of legs, particularly affecting the distal part. Accordingly, the leg disc was shrunken and frequently exhibited aberrant morphology. In addition, elevated Dlp levels induced ectopic cell death with no apparent cell proliferation changes. Furthermore, Dlp overexpression in the posterior compartment significantly altered Wingless (Wg) distribution. We observed a marked expansion of Wg distribution within the posterior compartment, accompanied by a corresponding decrease in the anterior compartment. It appears that excess Dlp guides Wg to diffuse to cells with higher Dlp levels. In addition, the distal-less (dll) gene, which is crucial for leg patterning, was up-regulated significantly. Notably, dachshund (dac) and homothorax (hth) expression, also essential for leg patterning and development, only appeared to be negligibly affected. Based on these findings, we speculate that excess Dlp may contribute to malformations of the distal leg region of Drosophila, possibly through its influence on Wg distribution, dll expression and induced cell death. Our research advances the understanding of Dlp function in Drosophila leg development. [ABSTRACT FROM AUTHOR]

Regeneration is a response mechanism aimed to restore tissues that have been damaged. We are studying in the wing disc of Drosophila the regenerative response to a dose of Ionizing Radiation that kills over 35% of the cells distributed all over the disc. After such treatment the discs are able to restore normal size, indicating there is a mechanism that repairs generalised damage. We have tested the role of the JNK, JAK/STAT and Wg pathways, known to be required for regeneration after localised damage in the disc. We find that after irradiation there is size compensation in the absence of function of these pathways, indicating that they are not necessary for the compensation. Furthermore, we also find that generalised damage does not cause an increase in the proliferation rate of surviving cells. We propose that irradiated discs suffer a developmental delay and resume growth at normal rate until they reach the final stereotyped size. The delay appears to be associated with a developmental reversion, because discs undergo rejuvenation towards an earlier developmental stage. We argue that the response to generalized damage is fundamentally different from that to localized damage, which requires activity of JNK and Wg. [ABSTRACT FROM AUTHOR]

During organogenesis cellular homeostasis plays a crucial role in patterning and growth. The role of promoter proximal pausing of RNA polymerase II, which regulates transcription of several developmental genes by GAGA factor or Motif 1 Binding Protein (M1BP), has not been fully understood in cellular homeostasis. Earlier, we reported that M1BP, a functional homolog of ZKSCAN3, regulates wingless (wg) and caspase-dependent cell death (apoptosis) in the Drosophila eye. Further, blocking apoptosis does not fully rescue the M1BPRNAi phenotype of reduced eye. Therefore, we looked for other possible mechanism(s). In a forward genetic screen, members of the Jun-amino-terminal-(NH2)-Kinase (JNK) pathway were identified. Downregulation of M1BP ectopically induces JNK, a pro-death pathway, known to activate both apoptosis and caspase-independent (autophagy) cell death. Activation of JNK pathway components can enhance M1BPRNAi phenotype and vice-versa. Downregulation of M1BP ectopically induced JNK signaling, which leads to apoptosis and autophagy. Apoptosis and autophagy are regulated independently by their genetic circuitry. Here, we found that blocking either apoptosis or autophagy alone rescues the reduced eye phenotype of M1BP downregulation; whereas, blocking both apoptosis and autophagy together significantly rescues the M1BP reduced eye phenotype to near wild-type in nearly 85% progeny. This data suggests that the cellular homeostasis response demonstrated by two independent cell death mechanisms, apoptosis and autophagy, can be regulated by a common transcriptional pausing mechanism orchestrated by M1BP. Since these fundamental processes are conserved in higher organisms, this novel functional link between M1BP and regulation of both apoptosis and autophagy can be extrapolated to humans. Abbreviations: hid: head involution defective; rpr: reaper; DIAP: Drosophila inhibitor of apoptosis proteins; RD genes: Retinal Determination genes; MF: Morphogenetic Furrow; PCD: Programmed cell death; ER: Endoplasmic reticulum; Wg: Wingless; JNK - c: Jun amino-terminal (NH2) Kinase; MAPKs – Mitogen: activated protein kinases; TNF: Tumor necrosis factor; Egr: Eiger; Wgn: Wengen; Tak 1: TGFβ activating kinase 1; JNKKK: JNK kinase kinase; Hep: Hemipterous; JNKK: JNK kinase; Bsk: Basket; Puc - Puckered; Pol II - RNA polymerase II; DNA: Deoxyribonucleic acid; TSS: Transcription start site; ESCs: Embryonic stem cells; Hop: Hopscotch; Dpp: Decapentaplegic; GAF: GAGA factor; M1BP: Motif 1 Binding Protein; ZAD: Zinc-associated domain; ZKSCAN3 - Zinc finger with a SCAN and a KRAB domain 3 (ZKSCAN3); UAS: Upstream activation sequence; ELAV: Embryonic lethal abnormal vision; RT qPCR: Real time quantitative polymerase chain reaction; LOF: Loss of function; GOF: Gain of function; GFP: Green fluorescent protein; WT: Wild-type; PBS: Phosphate buffered saline; PFA: Paraformaldehyde; PBST: Phosphate Buffered Saline with Triton X-100; β-GAL: Beta-galactosidase; DSHB: Developmental Studies Hybridoma Bank; CST: Cell Signaling Technologies; Dlg: Discs large; IgG: Immunoglobulin G; FITC: Fluorescein isothiocyanate; RNA: Ribonucleic acid; cDNA: Complementary DNA; Ct: cycle threshold; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; SAPK: Stress-activated protein kinases; HRP: Horse Radish Peroxidase; ROI: Region Of Interest; SEM: Standard Error of the Mean; CI: Confidence Intervals

BACKGROUND: Plant protein is widely used in the study of animal protein substitutes and healthy sustainable products. The gel properties are crucial for the production of plant protein foods. Therefore, the present study investigated the use of soybean oil to modulate the gel properties of soybean protein isolation‐wheat gluten composite with or without CaCl2. RESULTS: Oil droplets filled protein network pores under the addition of soybean oil (1–2%). This resulted in an enhanced gel hardness and water holding capacity. Further addition of soybean oil (3–4%), oil droplets and some protein–oil compounds increased the distance between the protein molecule chain. The results of Fourier transform infrared spectroscopy and intermolecular interaction also showed that the disulfide bond and β‐sheet ratio decreased in the gel system, which damaged the overall structure of the gel network. Compared with the addition of 0 m CaCl2, salt ion reduced the electrostatic repulsion between proteins, and local protein cross‐linking was more intense at 0.005 m CaCl2 concentration. In the present study, structural properties and rheological analysis showed that the overall strength of the gel was weakened after the addition of CaCl2. CONCLUSION: The presence of appropriate amount of soybean oil can fill the gel pores and improve the texture properties and network structure of soy protein isolate‐wheat gluten (SPI‐WG) composite gel. Excessive soybean oil may hinder protein–protein interaction and adversely affect protein gel. In addition, the presence or absence of CaCl2 significantly affected the gelling properties of SPI‐WG composite protein gels. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

BACKGROUND: Plant protein is widely used in the study of animal protein substitutes and healthy sustainable products. The gel properties are crucial for the production of plant protein foods. Therefore, the present study investigated the use of soybean oil to modulate the gel properties of soybean protein isolation‐wheat gluten composite with or without CaCl2. RESULTS: Oil droplets filled protein network pores under the addition of soybean oil (1–2%). This resulted in an enhanced gel hardness and water holding capacity. Further addition of soybean oil (3–4%), oil droplets and some protein–oil compounds increased the distance between the protein molecule chain. The results of Fourier transform infrared spectroscopy and intermolecular interaction also showed that the disulfide bond and β‐sheet ratio decreased in the gel system, which damaged the overall structure of the gel network. Compared with the addition of 0 m CaCl2, salt ion reduced the electrostatic repulsion between proteins, and local protein cross‐linking was more intense at 0.005 m CaCl2 concentration. In the present study, structural properties and rheological analysis showed that the overall strength of the gel was weakened after the addition of CaCl2. CONCLUSION: The presence of appropriate amount of soybean oil can fill the gel pores and improve the texture properties and network structure of soy protein isolate‐wheat gluten (SPI‐WG) composite gel. Excessive soybean oil may hinder protein–protein interaction and adversely affect protein gel. In addition, the presence or absence of CaCl2 significantly affected the gelling properties of SPI‐WG composite protein gels. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Regeneration is a response mechanism aimed to restore tissues that have been damaged. We are studying in the wing disc of Drosophila the regenerative response to a dose of Ionizing Radiation that kills over 35% of the cells distributed all over the disc. After such treatment the discs are able to restore normal size, indicating there is a mechanism that repairs generalised damage. We have tested the role of the JNK, JAK/STAT and Wg pathways, known to be required for regeneration after localised damage in the disc. We find that after irradiation there is size compensation in the absence of function of these pathways, indicating that they are not necessary for the compensation. Furthermore, we also find that generalised damage does not cause an increase in the proliferation rate of surviving cells. We propose that irradiated discs suffer a developmental delay and resume growth at normal rate until they reach the final stereotyped size. The delay appears to be associated with a developmental reversion, because discs undergo rejuvenation towards an earlier developmental stage. We argue that the response to generalized damage is fundamentally different from that to localized damage, which requires activity of JNK and Wg.

Abstract Background High mobility group protein B2 (HMGB2) is a multifunctional protein that plays various roles in different cellular compartments. Moreover, HMGB2 serves as a potential prognostic biomarker and therapeutic target for lung adenocarcinoma (LUAD). Methods In this study, the expression pattern, prognostic implication, and potential role of HMGB2 in LUAD were evaluated using the integrated bioinformatics analyses based on public available mRNA expression profiles from The Cancer Genome Atlas and Gene Expression Omnibus databases, both at the single-cell level and the tissue level. Further study in the patient-derived samples was conducted to explore the correlation between HMGB2 protein expression levels with tissue specificity, (tumor size-lymph node-metastasis) TNM stage, pathological grade, Ki-67 status, and overall survival. In vitro experiments, such as CCK-8, colony-formation and Transwell assay, were performed with human LUAD cell line A549 to investigate the role of HMGB2 in LUAD progression. Furthermore, xenograft tumor model was generated with A549 in nude mice. Results The results showed that the HMGB2 expression was higher in the LUAD samples than in the adjacent normal tissues and was correlated with high degree of malignancy in different public data in this study. Besides, over-expression of HMGB2 promoted A549 cells proliferation and migration while knocking down of HMGB2 suppressed the tumor promoting effect. Conclusions Our study indicated that HMGB2 was remarkably highly expressed in LUAD tissues, suggesting that it is a promising diagnostic and therapeutic marker for LUAD in the future.

Abnormal pain has recently been estimated to affect ∼50 million adults each year within the United States. With many treatment options for abnormal pain, such as opioid analgesics, carrying numerous deleterious side effects, research into safer and more effective treatment options is crucial. To help elucidate the mechanisms controlling nociceptive sensitivity, the Drosophila melanogaster larval nociception model has been used to characterize well-conserved pathways through the use of genetic modification and/or injury to alter the sensitivity of experimental animals. Mammalian models have provided evidence of β-catenin signaling involvement in neuropathic pain development. By capitalizing on the conserved nature of β-catenin functions in the fruit fly, here we describe a role for Armadillo, the fly homolog to mammalian β-catenin, in regulating baseline sensitivity in the primary nociceptor of the fly, in the absence of injury, using under- and over-expression of Armadillo in a cell-specific manner. Underexpression of Armadillo resulted in hyposensitivity, while overexpression of wild-type Armadillo or expression of a degradation-resistant Armadillo resulted in hypersensitivity. Neither underexpression nor overexpression of Armadillo resulted in observed dendritic morphological changes that could contribute to behavioral phenotypes observed. These results showed that focused manipulation of Armadillo expression within the nociceptors is sufficient to modulate baseline response in the nociceptors to a noxious stimulus and that these changes are not shown to be associated with a morphogenetic effect. [ABSTRACT FROM AUTHOR]

Background: High mobility group protein B2 (HMGB2) is a multifunctional protein that plays various roles in different cellular compartments. Moreover, HMGB2 serves as a potential prognostic biomarker and therapeutic target for lung adenocarcinoma (LUAD).Methods: In this study, the expression pattern, prognostic implication, and potential role of HMGB2 in LUAD were evaluated using the integrated bioinformatics analyses based on public available mRNA expression profiles from The Cancer Genome Atlas and Gene Expression Omnibus databases, both at the single-cell level and the tissue level. Further study in the patient-derived samples was conducted to explore the correlation between HMGB2 protein expression levels with tissue specificity, (tumor size-lymph node-metastasis) TNM stage, pathological grade, Ki-67 status, and overall survival. In vitro experiments, such as CCK-8, colony-formation and Transwell assay, were performed with human LUAD cell line A549 to investigate the role of HMGB2 in LUAD progression. Furthermore, xenograft tumor model was generated with A549 in nude mice.Results: The results showed that the HMGB2 expression was higher in the LUAD samples than in the adjacent normal tissues and was correlated with high degree of malignancy in different public data in this study. Besides, over-expression of HMGB2 promoted A549 cells proliferation and migration while knocking down of HMGB2 suppressed the tumor promoting effect.Conclusions: Our study indicated that HMGB2 was remarkably highly expressed in LUAD tissues, suggesting that it is a promising diagnostic and therapeutic marker for LUAD in the future. [ABSTRACT FROM AUTHOR]

Morphogen-mediated signaling is critical for proper organ development and stem cell function, and well-characterized mechanisms spatiotemporally limit the expression of ligands, receptors, and ligand-binding cell-surface glypicans. Here, we show that in the developing Drosophila ovary, canonical Wnt signaling promotes the formation of somatic escort cells (ECs) and their protrusions, which establish a physical permeability barrier to define morphogen territories for proper germ cell differentiation. The protrusions shield germ cells from Dpp and Wingless morphogens produced by the germline stem cell (GSC) niche and normally only received by GSCs. Genetic disruption of EC protrusions allows GSC progeny to also receive Dpp and Wingless, which subsequently disrupt germ cell differentiation. Our results reveal a role for canonical Wnt signaling in specifying the ovarian somatic cells necessary for germ cell differentiation. Additionally, we demonstrate the morphogen-limiting function of this physical permeability barrier, which may be a common mechanism in other organs across species.

Weather data is profoundly an important input for crop simulation models and soil and water management models. However, the metrological data cannot be easily accessed and sometimes it may be time consuming and costly. Validated climate models are needed to produces meteorological information for a given locations and altitudes. This study is designed to describe the temporal trends and spatial distribution of long-term weather data, to validate and test the performance of different weather generator tools, and to select the best-fit weather generator tools. Long-term climatic data (1990-2020) from the three agro ecologies of North Shewa was collected. In validation procedures, statistical indicators like mean, RMSE, CV, Correlation, and Regression analysis was done. The spatial Variability of Rainfall and minimum temperature is higher, having a coefficient of variability of nearly above 30%. As the analysis of PCI, the rainfall distribution shows a bimodal nature from March to May and July to September in all stations. From Man Kendall trend analysis, rainfall has decreasing trends, while maximum and minimum temperatures have increasing trends. The correlation coefficient for maximum temperature and minimum temperature in NASA and NewlocClim was found to be higher (> 80 %) at all stations. In general, the best-fit tools for temperature and rainfall data generations are NewLocClim and NASA. Therefore, from this study for rainfall data generation one may use NASA and NewLocClim for reproducing maximum and minimum reproducing over location. [ABSTRACT FROM AUTHOR]

The Decapentaplegic (Dpp) and Wingless (Wg) signal pathways play important roles in numerous biological processes in Drosophila. The Drosophila vestigial (vg) gene is selectively required for wing imaginal disc cell proliferation, which is essential for the formation of the adult wing and halter structures, and is regulated by Dpp and Wg signaling. Using a Drosophila invasion model of wing epithelium, we showed herein that inhibition of Dpp or Wg signaling promoted cells to migrate across the cell lineage restrictive anterior/posterior (A/P) compartment boundary. Being downstream of both Dpp and Wg signaling, vg can block cell migration induced by loss of either pathway. In addition, suppression of vg is sufficient to induce cell migration across the A/P boundary. Transcriptomic analysis revealed potential downstream genes involved in the cell migration after suppressing vg in the wing disc. We further demonstrated that the c‐Jun N‐terminal kinase (JNK) signaling promoted cell migration induced by vg suppression by upregulating Caspase activity. Taken together, our results revealed the requirement of Vg for suppressing cell migration and clarified how developmental signals collaborate to stabilize cells along the compartment boundary. [ABSTRACT FROM AUTHOR]

Dynein is a multi-subunit motor protein that moves toward the minus-end of microtubules, and plays important roles in fly development. We identified Dhc64Cm115, a new mutant allele of the fly Dynein heavy chain 64C (Dhc64C) gene whose heterozygotes survive against lethality induced by overexpression of Sol narae (Sona). Sona is a secreted metalloprotease that positively regulates Wingless (Wg) signaling, and promotes cell survival and proliferation. Knockdown of Dhc64C in fly wings induced extensive cell death accompanied by widespread and disorganized expression of Wg. The disrupted pattern of the Wg protein was due to cell death of the Wg-producing cells at the DV midline and overproliferation of the Wg-producing cells at the hinge in disorganized ways. Coexpression of Dhc64C RNAi and p35 resulted in no cell death and normal pattern of Wg, demonstrating that cell death is responsible for all phenotypes induced by Dhc64C RNAi expression. The effect of Dhc64C on Wg-producing cells was unique among components of Dynein and other microtubule motors. We propose that Dhc64C differentially regulates survival of Wg-producing cells, which is essential for maintaining normal expression pattern of Wg for wing development.

Graphical abstract Abstract Autophagy-dependent cell death is a distinct mode of regulated cell death required in a context specific manner. One of the best validated genetic models of autophagy-dependent cell death is the removal of the Drosophila larval midgut during larval-pupal transition. We have previously shown that down-regulation of growth signaling is essential for autophagy induction and larval midgut degradation. Sustained growth signaling through Ras and PI3K blocks autophagy and consequently inhibits midgut degradation. In addition, the morphogen Dpp plays an important role in regulating the correct timing of midgut degradation. Here we explore the potential roles of Hh and Wg signaling in autophagy-dependent midgut cell death. We demonstrate that Hh and Wg signaling are not involved in the regulation of autophagy-dependent cell death. However, surprisingly we found that one key component of these pathways, the Drosophila Glycogen Synthase Kinase 3, Shaggy (Sgg), may regulate midgut cell size independent of Hh and Wg signaling. [ABSTRACT FROM AUTHOR]

Morphogens are signaling molecules produced by a localized source, specifying cell fate in a graded manner. The source secretes morphogens into the extracellular milieu to activate various target genes in an autocrine or paracrine manner. Here we describe various secreted forms of two canonical morphogens, the lipid-anchored Hedgehog (Hh) and Wnts, indicating the involvement of multiple carriers in the transport of these morphogens. These different extracellular secreted forms are likely to have distinct functions. Here we evaluate newly identified mechanisms that morphogens use to traverse the required distance to activate discrete paracrine signaling. [ABSTRACT FROM AUTHOR]

Tissue patterning, through the concerted activity of a small number of signaling pathways, is critical to embryonic development. While patterning can involve signaling between neighbouring cells, in other contexts signals act over greater distances by traversing complex cellular landscapes to instruct the fate of distant cells. In this review, we explore different strategies adopted by cells to modulate signaling molecule range to allow correct patterning. We describe mechanisms for restricting signaling range and highlight how such short-range signaling can be exploited to not only control the fate of adjacent cells, but also to generate graded signaling within a field of cells. Other strategies include modulation of signaling molecule action by tissue architectural properties and the use of cellular membranous structures, such as signaling filopodia and exosomes, to actively deliver signaling ligands to target cells. Signaling filopodia can also be deployed to reach out and collect particular signals, thereby precisely controlling their site of action. [ABSTRACT FROM AUTHOR]

Wind generation (WG) is the most widespread renewable energy resource in the world. However, this implementation inevitably leads to an increase in the problems caused by WG, e.g. frequency oscillations, power fluctuations or voltage variations. To overcome these problems, the use of a power conditioning system (PCS) coupled with a vanadium redox flow battery (VRFB) is proposed in this study. The PCS is composed of a distribution static synchronous compensator connected to a dc/dc chopper. The PCS/VRFB detailed model is presented and a three‐level control system is developed. This control system allows the PCS/VRFB to perform a decoupled reactive and active power flow control. The dynamic response of the PCS/VRFB is evaluated through simulation tests, and performance characteristics of the device are obtained by means of the variation of the power references. The results obtained demonstrate that the PCS/VRFB offers a good transient response and the control system proposed allows mitigating the problems caused by wind power generation. [ABSTRACT FROM AUTHOR]

This article introduces a weak Galerkin (WG) finite element method for quad-curl problems in three dimensions. It is proved that the proposed WG method is stable and accurate in an optimal order of error estimates for the exact solution in discrete norms. In addition, an L 2 error estimate in an optimal order except the lowest order k = 2 is derived for the WG solution. Some numerical experiments are conducted to verify the efficiency and accuracy of our WG method and furthermore a superconvergence has been observed from the numerical results. [ABSTRACT FROM AUTHOR]

Many adult tissues and organs are maintained by resident stem cells that are activated in response to injury but the mechanisms that regulate stem cell activity during regeneration are still poorly understood. An emerging system to study such problem is the Drosophila adult midgut. Recent studies have identified both intrinsic factors and extrinsic niche signals that control the proliferation, self-renewal, and lineage differentiation of Drosophila adult intestinal stem cells (ISCs). These findings set up the stage to interrogate how niche signals are regulated and how they are integrated with cell-intrinsic factors to control ISC activity during normal homeostasis and regeneration. Here we review the current understanding of the mechanisms that control ISC self-renewal, proliferation, and lineage differentiation in Drosophila adult midgut with a focus on the niche signaling network that governs ISC activity in response to injury. [ABSTRACT FROM AUTHOR]

This article introduces a weak Galerkin (WG) finite element method for linear elasticity interface problems on general polygonal/polyhedral partitions. The discrete weak divergence and gradient operators are discretized as polynomials and computed by solving inexpensive local problems on each element. The developed WG method has been proved to be stable and accurate with optimal order error estimates in the discrete H 1 norm. Some numerical experiments are conducted to verify the efficiency and accuracy of the proposed WG method, in addition, and its uniform convergence independent of the jump of the interface coefficients and the incompressibility. [ABSTRACT FROM AUTHOR]

Neurons require target-derived autocrine and paracrine growth factors to maintain proper identity, innervation, homeostasis and survival. Neuronal growth factor signaling is highly dependent on membrane traffic, both for the packaging and release of the growth factors themselves, and for regulation of intracellular signaling by their transmembrane receptors. Here, we review recent findings from the Drosophila larval neuromuscular junction ( NMJ) that illustrate how specific steps of intracellular traffic and inter-organelle interactions impinge on signaling, particularly in the bone morphogenic protein, Wingless and c-Jun-activated kinase pathways, regulating elaboration and stability of NMJ arbors, construction of synapses and synaptic transmission and homeostasis. These membrane trafficking and signaling pathways have been implicated in human motor neuron diseases including amyotrophic lateral sclerosis and hereditary spastic paraplegia, highlighting their importance for neuronal health and survival. [ABSTRACT FROM AUTHOR]

The well-known Welch-Gong (WG) stream cipher, proposed by Nawaz and Gong in 2005, was submitted to the hardware profile of the eSTREAM project. In the last several years, the original WGhas come under several cryptanalytic attacks. However, as for the final version ofWG, no attack has been published on it until now. In this paper, an efficient key recovery attack on the final WG stream cipher in the related key setting is proposed. Under related keys, we can recover the 128-bit secret key of WG-128 with a time complexity of 289 and a memory complexity of 245. The success probability of the attack is 0.6321. This result shows that our attack on WG-128 is much better than an exhaustive key search in the related key setting. Furthermore, our cryptanalytic results show that WG with IV size no less than 80 bits is vulnerable to a related key attack. The main feature of our attack is that it is independent of the number of steps in the key/IV setup ofWG, and then increasing the number of steps in the key/IV setup cannot strengthen the resistance of WG against a related key attack. Finally, a recommended approach to repair the weakness and strengthen the resistance of WG against a related key attack is presented. [ABSTRACT FROM AUTHOR]

In this paper, we develop a modified weak Galerkin finite element method on arbitrary grids for convection-diffusion problems in two dimensions based on our previous work (Wang et al., J Comput Appl Math 271, 319-327, ), in which we only considered second order Poisson equations and thus only introduced a modified weak gradient operator. This method, called MWG-FEM, is based on a modified weak gradient operator and weak divergence operator which is put forward in this paper. Optimal order error estimates are established for the corresponding MWG-FEM approximations in both a discrete $$H^1$$ norm and the standard $$L^2$$ norm. Numerical results are presented to demonstrate the robustness, reliability, and accuracy of the MWG-FEM. [ABSTRACT FROM AUTHOR]

Anti-neutrophil cytoplasmic antibody (ANCA) are produced against lysozomal constituents and primary granules of myeloid cells (Neutrophiles & monocytes) in some rheumatic diseases and wegner’s granulomtosis (WG). This antibodies not only may related to onset of vasculitis lesions, but also have a valuable diagnostic tool, thus, first we tired to evaluated the prevalence of this antibodies in 65 serum of patients with RA and 42 serum of patients with SLE. By using of indirect immunoflourescence assay (IFA), two staining patterns are recognized: Cytoplasmic (C-ANCA) pattern which in 80% of results from anti-PR3, and prenuclear (P-ANCA) pattern, which can result from any antibody directed to myeloperoxidase (MPO), cathepsin G (CG) lactoferrin (LF), elastsae (HLE) and lysozyme (LZ). The sensitivity and specificity for SLE from 1:128 serum dilution was 8% and 85.1% respectively, and for RA from 1:16 dilution was 32.2% and 87.5% respectively. Of the 19 SLE, ANCA positive patients 18 (94.7%) had P-ANCA and 1 patient (5.3%) had C-ANCA and of the 23 RA, ANCA positive patients, 17 (73.9%) had P-ANCA and 6 patients (26.1%) had C-ANCA.

When taking up the gauntlet of studying membrane protein functionality, scientists are provided with a plethora of advantages, which can be exploited for the synthesis of these difficult‐to‐express proteins by utilizing cell‐free protein synthesis systems. Due to their hydrophobicity, membrane proteins have exceptional demands regarding their environment to ensure correct functionality. Thus, the challenge is to find the appropriate hydrophobic support that facilitates proper membrane protein folding. So far, various modes of membrane protein synthesis have been presented. Here, we summarize current state‐of‐the‐art methodologies of membrane protein synthesis in biomimetic‐supported systems. The correct folding and functionality of membrane proteins depend in many cases on their integration into a lipid bilayer and subsequent posttranslational modification. We highlight cell‐free systems utilizing the advantages of biological membranes. [ABSTRACT FROM AUTHOR]

Voltage scaling can reduce power dissipation significantly. SRAM cells (which are traditionally implemented by using six‐transistor cells) can limit voltage scaling because of stability concerns. Eight‐transistor (8T) cells were proposed to enhance cell stability under voltage scaling. 8T cells, however, suffer from costly write operations caused by the column selection issue. A proposed technique, Read‐Modify‐Write (RMW), addresses this issue at the expense of extra read operations. The extra cache access affects performance and power dissipation negatively. In this study, the authors show that a large share of the cache accesses in RMW is unnecessary. To address this inefficiency, they propose two micro‐architectural solutions with the aim of reducing the overhead imposed by RMW. The authors first proposed technique, Write Grouping (WG), relies on a buffering mechanism that identifies the redundant and the unnecessary cache accesses imposed by RMW and eliminates them. Their second technique, WG and Read Bypassing (WG + RB), improves the WG's efficiency further at a negligible area cost. Their simulation results show that on average, WG and WG + RB reduce RMW's cache traffic overhead by 15% and 20%, respectively. They show that WG and WG + RB also improve average performance by 30% and 37%, respectively. [ABSTRACT FROM AUTHOR]

Background: Hox genes encode transcription factors playing important role in segment specific morphogenesis along the anterior posterior axis. Most work in the Hox field aimed at understanding the basis for specialised Hox functions, while little attention was given to Hox common function. In Drosophila, genes of the Bithorax complex [ Ultrabithorax ( Ubx), abdominalA ( abdA), and AbdominalB ( AbdB)] all promote abdominal identity. While Ubx and AbdA share extensive sequence conservation, AbdB is highly divergent, questioning how it can perform similar functions as Ubx and AbdA. Results: In this study, we investigate the genetic requirement for the specification of abdominal-type denticles by Ubx, AbdA, and AbdB. The impact of ectopic expression of Hox proteins in embryos mutant for Exd as well as of Wingless or Hedgehog signaling involved in intrasegmental patterning was analyzed. Results indicated that Ubx and AbdA do not require Exd, Wg, and Hh activity for specifying abdominal-type denticles, while AbdB does. Conclusions: Our results support that distinct regulatory mechanisms underlie Ubx/AbdA- and AbdB-mediated specification of abdominal-type denticles, highlighting distinct strategies for achieving a similar biological output. This suggests that common function performed by distinct paralogue Hox proteins may also rely on newly acquired property, instead of conserved/ancestral properties. Developmental Dynamics 243:192-200, 2014. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Abstract: JAK/STAT signaling is localized to the wing hinge, but its function there is not known. Here we show that the Drosophila STAT Stat92E is downstream of Homothorax and is required for hinge development by cell-autonomously regulating hinge-specific factors. Within the hinge, Stat92E activity becomes restricted to gap domain cells that lack Nubbin and Teashirt. While gap domain cells lacking Stat92E have significantly reduced proliferation, increased JAK/STAT signaling there does not expand this domain. Thus, this pathway is necessary but not sufficient for gap domain growth. We show that reduced Wingless (Wg) signaling dominantly inhibits Stat92E activity in the hinge. However, ectopic JAK/STAT signaling does not perturb Wg expression in the hinge. We report negative interactions between Stat92E and the notum factor Araucan, resulting in restriction of JAK/STAT signaling from the notum. In addition, we find that the distal factor Nub represses the ligand unpaired as well as Stat92E activity. These data suggest that distal expansion of JAK/STAT signaling is deleterious to wing blade development. Indeed, mis-expression of Unpaired within the presumptive wing blade causes small, stunted adult wings. We conclude that JAK/STAT signaling is critical for hinge fate specification and growth of the gap domain and that its restriction to the hinge is required for proper wing development. [Copyright &y& Elsevier]

Abstract: Morphogens control developmental decisions by regulating the expression of different sets of target genes in specific regions. The products of these genes drive the region specific developmental program and lead to the formation of different adult structures. Therefore, identification of the morphogens downstream target effectors is an essential step in deciphering the mechanisms underlying organ development. In the Drosophila developing wing, signaling by the morphogens Decapentaplegic (Dpp) and Wingless (Wg) plays global roles in controlling differentiation, growth, and survival. However, only a handful of their downstream target genes have been identified. Here, we describe a screening method designed to quickly search through large collections of P-Gal4 enhancer-traps for candidate genes that are transcriptionally regulated by Dpp or Wg signaling. Using this screening method, we screened a small collection of lethal P-Gal4 insertion lines that are expressed in the wing disc. We identified 10 novel putative Dpp and/or Wg target genes in the developing wing. Further study of the roles of the genes recognized in this screen should shed light on how morphogens control various processes in organ development. [Copyright &y& Elsevier]

Abstract: Biomedical implants are generally coated with a thin layer of hydroxyapatite (HA) using a plasma spraying or pulsed laser deposition method. However, the bonding strength between the coating layer and the substrate is relatively low. Moreover, the high temperature of the deposition process causes a structural instability of the HA, and therefore degrades its bioactivity and reduces the service life of the coating layer following implantation. Accordingly, the present study replaces HA with fluorapatite (FA) as the coating material, and examines the effects of two different binders, namely polyvinyl alcohol (PVA) and water glass (WG), on the properties of FA coatings deposited on Ti–6Al–4V substrates using an Nd-YAG laser cladding process. Scanning electron microscopy (SEM) observations reveal that the FA coating has a coral- and dendrite-like structure when mixed with the PVA binder, but a pure dendrite-like structure when mixed with the WG binder. In addition, the Ca/P value of the WG-based FA coating is significantly higher than that of the PVA-based coating. Fluorapatite, Al2O3, CaTiO3 and Ca3(PO4)2 phases are observed in both coating layers. However, the XRD analysis results indicate that the microstructure of the WG sample is dominated by Ca3(PO4)2 phase while that of the PVA sample is dominated by FA. After soaking in SBF, it was observed that the specimen produced with PVA binder or less laser output power possessed a better apatite induction ability. [ABSTRACT FROM AUTHOR]

Wg/Wnt signals specify cell fates in both invertebrate and vertebrate embryos and maintain stem-cell populations in many adult tissues. Deregulation of the Wnt pathway can transform cells to a proliferative fate, leading to cancer. We have discovered that two Drosophila proteins that are crucial for cytokinesis have a second, largely independent, role in restricting activity of the Wnt pathway. The fly homolog of RacGAP1, Tumbleweed (Tum)/RacGAP50C, and its binding partner, the kinesin-like protein Pavarotti (Pav), negatively regulate Wnt activity in fly embryos and in cultured mammalian cells. Unlike many known regulators of the Wnt pathway, these molecules do not affect stabilization of Arm/β-catenin (βcat), the principal effector molecule in Wnt signal transduction. Rather, they appear to act downstream of βcat stabilization to control target-gene transcription. Both Tum and Pav accumulate in the nuclei of interphase cells, a location that is spatially distinct from their cleavage-furrow localization during cytokinesis. We show that this nuclear localization is essential for their role in Wnt regulation. Thus, we have identified two modulators of the Wnt pathway that have shared functions in cell division, which hints at a possible link between cytokinesis and Wnt activity during tumorigenesis. [ABSTRACT FROM AUTHOR]

A species of aster leafhopper ( Macrosteles sp.) became established in 2001 on Oahu, Hawaii, and through the transmission of the aster yellows phytoplasma, caused devastating losses to the island’s watercress industry. DNA sequence data were analysed from two mitochondrial genes [cytochrome oxidase subunit 1( CO1) and nicotinamide adenine dinucleotide 1 ( NADH1)] and one nuclear gene (wingless, Wg) (combined total of 1874 bp) to reconstruct phylogenetic relationships between putative US mainland source populations of aster leafhoppers and those introduced to Hawaii. These data were applied to elucidate the origin(s) and identity of Hawaiian infestations and the amount of genetic diversity within introduced invasive populations. Both phylogenetic search criteria (Bayesian and maximum likelihood models) converged onto similar tree topologies for all three gene regions and suggested that Hawaii infestations represent a single undescribed leafhopper species unrelated to the common aster leafhopper, Macrosteles quadrilineatus. An exact haplotype match was found from a specimen intercepted from watercress shipped to Hawaii from Los Angeles, California, suggesting this region as the potential source for Hawaiian infestations. Two mitochondrial haplotypes were identified in Hawaii suggesting two or perhaps just a single introduction of more than one female. [ABSTRACT FROM AUTHOR]

The Drosophila melanogaster gene Anaplastic Lymphoma Kinase ( Alk) regulates a signal transduction pathway required for founder cell specification within the visceral muscle of the developing embryonic midgut. During embryonic development, the midgut visceral muscle is lined by the endodermal cell layer. In this paper, we have investigated signalling between these two tissues. Here, we show that Alk function is required for decapentaplegic (Dpp) expression and subsequent signalling via the Mad pathway in the developing gut. We propose that not only does Alk signalling regulate founder cell specification and thus fusion in the developing visceral muscle, but that Alk also regulates Dpp signalling between the visceral muscle and the endoderm. This provides an elegant mechanism with which to temporally coordinate visceral muscle fusion and later events in midgut development. [ABSTRACT FROM AUTHOR]

Abstract: The late-third-instar labial disc is comprised of two disc-proper cell layers, one representing mainly the ventral half of the anterior compartment (L-layer) and the other, the dorsal half of the anterior compartment and most, if not all, of the posterior compartment (M-layer). In the L-layer, Distal-less represses homothorax whereas no Distal-less-dependent homothorax repression occurs in the M-layer where Distal-less is coexpressed with homothorax. In wild-type labial discs, clawless, one of the two homeobox genes expressed in distal cells receiving maximum (Decapentaplegic+Wingless) signaling activity in leg and antennal discs, is specifically repressed by proboscipedia. A fate map, inferred from data on basic patterning gene expression in larval and pupal stages and mutant phenotypes, indicates the inner surface of the labial palpus, which includes the pseudotracheal region, to be a derivative of the distal portion of the M-layer expressing wingless, patched, Distal-less and homothorax. The outer surface of the labial palpus with more than 30 taste bristles derives from an L-layer area consisting of dorsal portions of the anterior and posterior compartments, each expressing Distal-less. Our analysis also indicates that, in adults and pupae, the anterior–posterior boundary, dividing roughly equally the outer surface of the distiproboscis, runs along the outer circumference of the inner surface of distiproboscis. [Copyright &y& Elsevier]

Abstract: The Wingless (Wg)/Wnt signaling pathway regulates a myriad of developmental processes and its malfunction leads to human disorders including cancer. Recent studies suggest that casein kinase I (CKI) family members play pivotal roles in the Wg/Wnt pathway. However, genetic evidence for the involvement of CKI family members in physiological Wg/Wnt signaling events is lacking. In addition, there are conflicting reports regarding whether a given CKI family member functions as a positive or negative regulator of the pathway. Here we examine the roles of seven CKI family members in Wg signaling during Drosophila limb development. We find that increased CKIε stimulates whereas dominant-negative or a null CKIε mutation inhibits Wg signaling. In contrast, inactivation of CKIα by RNA interference (RNAi) leads to ectopic Wg signaling. Interestingly, hypomorphic CKIε mutations synergize with CKIα RNAi to induce ectopic Wg signaling, revealing a negative role for CKIε. Conversely, CKIα RNAi enhances the loss-of-Wg phenotypes caused by CKIε null mutation, suggesting a positive role for CKIα. While none of the other five CKI isoforms can substitute for CKIα in its inhibitory role in the Wg pathway, several CKI isoforms including CG12147 exhibit a positive role based on overexpression. Moreover, loss of Gilgamesh (Gish)/CKIγ attenuates Wg signaling activity. Finally, we provide evidence that several CKI isoforms including CKIα and Gish/CKIγ can phosphorylate the Wg coreceptor Arrow (Arr), which may account, at least in part, for their positive roles in the Wg pathway. [Copyright &y& Elsevier]

The egg-pathogenic fungus Paecilomyces lilacinus strain 251 (PL215) was investigated under different temperature regimes for biocontrol activity against the northern root-knot nematode Meloidogyne hapla. Biocontrol activity by PL251 was affected by temperature and initial nematode inoculum density. At 20/23°C (night/day) control efficacy reached 71% at a high inoculum density of 10 000 eggs and juveniles (E + J) per 500 cm3 compared to 65% control at the lower inoculum density (5000 E + J/500 cm3). By contrast, average efficacy was 5% and 46% at low and high inoculum levels, respectively, when temperatures were between 19°C and 21°C (night/day). A significant interaction between the factors inoculum density and treatment with PL251 was observed at low temperatures, when only few M. hapla galls and egg masses developed after inoculation with 5000 E + J/500 cm3. When the temperature was favourable for the fungal parasite (25°C), efficacy reached 90%. In glasshouse experiments with unfavourable temperatures for M. hapla development (25°C-33°C), tomato plants repeatedly treated with PL251 showed significantly higher fruit yield (23-102%). [ABSTRACT FROM AUTHOR]

Tissue induction during embryonic development relies to a significant degree on the integration of combinatorial regulatory inputs at the enhancer level of target genes. During mesodermal tissue induction in Drosophila, various combinations of inductive signals and mesoderm-intrinsic transcription factors cooperate to induce the progenitors of different types of muscle and heart precursors at precisely defined positions within the mesoderm layer. Dpp signals are required in cooperation with the mesoderm-specific NK homeodomain transcription factor Tinman (Tin) to induce all dorsal mesodermal tissue derivatives, which include dorsal somatic muscles, the dorsal vessel and visceral muscles of the midgut. Wingless (Wg) signals modulate the responses to Dpp/Tin along anteroposterior positions by cooperating with Dpp/Tin during dorsal vessel and somatic muscle induction while antagonizing Dpp/Tin during visceral mesoderm induction. As a result, dorsal muscle and cardiac progenitors form in a pattern that is reciprocal to that of visceral muscle precursors along the anteroposterior axis. Our present study addresses how positive Dpp signals and antagonistic Wg inputs are integrated at the enhancer level of bagpipe (bap), a NK homeobox gene that serves as an early regulator of visceral mesoderm development. We show that an evolutionarily conserved bap enhancer element requires combinatorial binding sites for Tin and Dpp-activated Smad proteins for its activity. Adjacent binding sites for the FoxG transcription factors encoded by the Sloppy paired genes (slp1 and slp2), which are direct targets of the Wg signaling cascade, serve to block the synergistic activity of Tin and activated Smads during bap induction. In addition, we show that binding sites for yet unknown repressors are essential to prevent the induction of the bap enhancer by Dpp in the dorsal ectoderm. Our data illustrate how the same signal combinations can have opposite effects on different targets in the... [ABSTRACT FROM AUTHOR]

Programmed cell death or apoptosis plays an important role in the development of multicellular organisms and can also be induced by various stress events. In the Drosophila wing imaginal disc there is little apoptosis in normal development but X-rays can induce high apoptotic levels, which eliminate a large fraction of the disc cells. Nevertheless, irradiated discs form adult patterns of normal size, indicating the existence of compensatory mechanisms. We have characterised the apoptotic response of the wing disc to X-rays and heat shock and also the developmental consequences of compromising apoptosis. We have used the caspase inhibitor P35 to prevent the death of apoptotic cells and found that it causes increased non autonomous cell proliferation, invasion of compartments and persistent misexpression of the wingless (wg) and decapentaplegic (dpp) signalling genes. We propose that a feature of cells undergoing apoptosis is to activate wg and dpp, probably as part of the mechanism to compensate for cell loss. If apoptotic cells are not eliminated, they continuously emit Wg and Dpp signals, which results in developmental aberrations. We suggest that a similar process of uncoupling apoptosis initiation and cell death may occur during tumour formation in mammalian cells. [ABSTRACT FROM AUTHOR]