Disrupted nuclear import of cell cycle proteins in Huntington's/PolyQ disease causes neurodevelopment defects in cellular and Drosophila model.

Huntington's disease is caused by an expansion of CAG repeats in exon 1 of the huntingtin gene encoding an extended PolyQ tract within the Huntingtin protein (mHtt). This expansion results in selective degeneration of striatal medium spiny projection neurons in the basal ganglia. The mutation causes abnormalities during neurodevelopment in human and mouse models. Here, we report that mHtt/PolyQ aggregates inhibit the cell cycle in the Drosophila brain during development. PolyQ aggregates disrupt the nuclear pore complexes of the cells preventing the translocation of cell cycle proteins such as Cyclin E, E2F and PCNA from cytoplasm to the nucleus, thus affecting cell cycle progression. PolyQ aggregates also disrupt the nuclear pore complex and nuclear import in mHtt expressing mammalian CAD neurons. PolyQ toxicity and cell cycle defects can be restored by enhancing RanGAP-mediated nuclear import, suggesting a potential therapeutic approach for this disease.

Expanded polyQ aggregates interact with sarco-endoplasmic reticulum calcium ATPase and Drosophila inhibitor of apoptosis protein1 to regulate polyQ mediated neurodegeneration in Drosophila.

Polyglutamine (polyQ) induced neurodegeneration is one of the leading causes of progressive neurodegenerative disorders characterized clinically by deteriorating movement defects, psychiatric disability, and dementia. Calcium [Ca2+] homeostasis, which is essential for the functioning of neuronal cells, is disrupted under these pathological conditions. In this paper, we simulated Huntington's disease phenotype in the neuronal cells of the Drosophila eye and identified [Ca2+] pump, sarco-endoplasmic reticulum calcium ATPase (SERCA), as one of the genetic modifiers of the neurodegenerative phenotype. This paper shows genetic and molecular interaction between polyglutamine (polyQ) aggregates, SERCA and DIAP1. We present evidence that polyQ aggregates interact with SERCA and alter its dynamics, resulting in a decrease in cytosolic [Ca2+] and an increase in ER [Ca2+], and thus toxicity. Downregulating SERCA lowers the enhanced calcium levels in the ER and rescues, morphological and functional defects caused due to expanded polyQ repeats. Cell proliferation markers such as Yorkie (Yki), Scalloped (Sd), and phosphatidylinositol 3 kinases/protein kinase B (PI3K/Akt), also respond to varying levels of calcium due to genetic manipulations, adding to the amelioration of degeneration. These results imply that neurodegeneration due to expanded polyQ repeats is sensitive to SERCA activity, and its manipulation can be an important step toward its therapeutic measures.

Tissue and Time Optimization for Real-Time Detection of Apple Mosaic Virus and Apple Necrotic Mosaic Virus Associated with Mosaic Disease of Apple (Malus domestica).

Besides apple mosaic virus (ApMV), apple necrotic mosaic virus (ApNMV) has also been found to be associated with apple mosaic disease. Both viruses are unevenly distributed throughout the plant and their titer decreases variably with high temperatures, hence requiring proper tissue and time for early and real-time detection within plants. The present study was carried out to understand the distribution and titer of ApMV and ApNMV in apple trees from different plant parts (spatial) during different seasons (temporal) for the optimization of tissue and time for their timely detection. The Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and Reverse Transcription-quantitative Polymerase Chain Reaction (RT-qPCR) was carried out to detect and quantify both viruses in the various plant parts of apple trees during different seasons. Depending on the availability of tissue, both ApMV and ApNMV were detected in all the plant parts during the spring season using RT-PCR. During the summer, both viruses were detected only in seeds and fruits, whereas they were detected in leaves and pedicel during the autumn season. The RT-qPCR results showed that during the spring, the ApMV and ApNMV expression was higher in leaves, whereas in the summer and autumn, the titer was mostly detected in seeds and leaves, respectively. The leaves in the spring and autumn seasons and the seeds in the summer season can be used as detection tissues through RT-PCR for early and rapid detection of ApMV and ApNMV. This study was validated on 7 cultivars of apples infected with both viruses. This will help to accurately sample and index the planting material well ahead of time, which will aid in the production of virus-free, quality planting material.

Undiagnosed Bilateral Avascular Necrosis of the Femur in a Young Male Caused by COVID-19 Steroid Injections.

Osteonecrosis is a degenerative bone disease brought on by a change in subchondral blood flow and characterized by the loss of bone cellular components. Other names for it include ischemic bone necrosis, aseptic necrosis, and avascular necrosis. Long bones' epiphyses in weight-bearing joints are typically impacted. In extreme cases, a joint may completely collapse or subchondral bone may be obliterated. Avascular necrosis, which most frequently affects joints, especially the femoral head, occurs when the blood supply to the bones is diminished. In this article, we will explain the clinical case of a 40-year-old man who's been complaining about hip pain for two months. The patient went to Acharya Vinobha Bhave Rural Hospital (AVBRH) with the same complaint and underwent some tests; upon inspection, it was discovered that the patient had bilateral avascular femoral head necrosis. For avascular necrosis (AVN) of the left femoral head, the patient had core decompression surgery. Once post-operative physical therapy was initiated, the condition significantly improved, and it also served to prevent additional abnormalities. The goal of this case study is to examine the therapeutic strategies essential for treating bilateral femoral head avascular necrosis.

Hsc70-4 aggravates PolyQ-mediated neurodegeneration by modulating NF-κB mediated immune response in Drosophila.

Huntington's disease occurs when the stretch of CAG repeats in exon 1 of the huntingtin (htt) gene crosses the permissible limit, causing the mutated protein (mHtt) to form insoluble aggregates or inclusion bodies. These aggregates are non-typically associated with various essential proteins in the cells, thus disrupting cellular homeostasis. The cells try to bring back normalcy by synthesizing evolutionary conserved cellular chaperones, and Hsp70 is one of the families of heat shock proteins that has a significant part in this, which comprises of heat-inducible and cognate forms. Here, we demonstrate that the heat shock cognate (Hsc70) isoform, Hsc70-4/HSPA8, has a distinct role in polyglutamate (PolyQ)-mediated pathogenicity, and its expression is enhanced in the polyQ conditions in Drosophila. Downregulation of hsc70-4 rescues PolyQ pathogenicity with a notable improvement in the ommatidia arrangement and near-normal restoration of optic neurons leading to improvement in phototaxis response. Reduced hsc70-4 also attenuates the augmented immune response by decreasing the expression of NF-κB and the antimicrobial peptides, along with that JNK overactivation is also restored. These lead to the rescue of the photoreceptor cells, indicating a decrease in the caspase activity, thus reverting the PolyQ pathogenicity. At the molecular level, we show the interaction between Hsc70-4, Polyglutamine aggregates, and NF-κB, which may be responsible for the dysregulation of signaling molecules in polyQ conditions. Thus, the present data provides a functional link between Hsc70-4 and NF-κB under polyQ conditions.

Ayurvedic formulations Guduchi and Madhuyashti triggers JNK signaling mediated immune response and adversely affects Huntington phenotype.

BACKGROUND: Huntington's disease manifests due to abnormal CAG trinucleotide expansion, in the first exon of the Huntingtin gene and disease progression involves genetic, immune, and environmental components. The pathogenesis is characterized by the formation of Inclusion Bodies, disruption of neuronal circuitry, cellular machinery, and apoptosis, resulting in gradual and progressive loss of neuronal cells, ultimately leading to nervous system dysfunction. Thus, the present study was conducted to assess the effect of two Ayurvedic formulations, Guduchi and Madhuyashti, on Huntington's phenotype, using Drosophila as a model system. METHOD: The Huntington phenotype was ectopically induced in the Drosophila eye using the UAS-GAL4 binary system and the effect of the two Ayurvedic formulations were assessed by feeding the progenies on them. Degeneration was observed microscopically and Real Time-PCR was done to assay the alterations in the different transcripts of the innate immune pathways and JNK signaling pathway. Immunostaining was performed to assay different gene expression patterns. RESULT: The present study shows that Guduchi and Madhuyashti, endowed with immunomodulatory and intellect promoting properties, aggravates polyQ mediated neurodegeneration. We provide evidence that these formulations enhance JNK signaling by activating the MAP 3 K, dTAK1, which regulates the expression of Drosophila homologue for JNK. Sustained, rather than a transient expression of JNK leads to excessive production of Anti-Microbial Peptides without involving the canonical transcription factors of the Toll or IMD pathways, NF-κB. Enhanced JNK expression also increases caspase levels, with a concomitant reduction in cell proliferation, which may further contribute to increased degeneration. CONCLUSION: This is a report linking the functional relevance of Guduchi and Madhuyashti with molecular pathways, which can be important for understanding their use in therapeutic applications and holds promise for mechanistic insight into the mammalian counterpart.

Physiotherapeutic Rehabilitation of a Patient With a Comminuted Displaced Iliac Fracture and Superior and Inferior Pubic Rami Fractures: A Case Report.

Ilium fractures, which commonly advance from the iliac crest to the greater sciatic notch, are high-energy pelvic fractures that are frequently unstable. The general course of management for this injury is conservative, although cases of substantially displaced have been described that warranted surgical intervention. Many conditions, including decreased mobility, structural alterations in the joints, and discomfort, might make people more vulnerable to falls while waiting for hip or knee surgery. This can have an effect on both preoperative and postoperative functioning. The goal of surgical treatment for these individuals is to return them back to their prefracture state. This article presents the case of a 30-year-old male who was obtained a dash injury while riding a motorbike. He was diagnosed by an orthopedic surgeon with right-sided iliac blade fracture extending towards sacroiliac joint with right-sided sacral ala fracture and superior pubic rami fracture extending toward iliopectineal line and right-sided inferior pubic rami fracture (Tile Classification Type B3). He was operated via open reduction and internal fixation (ORIF) with osteosynthesis plating was done. Following surgery, the patient was dependent and his daily living was hampered. However, physiotherapy intervention improved the patient's pain and physical functioning and he gained independence in carrying out daily activities.

Identification and multilocus gene characterization of phytoplasmas associated with sweet cherry in India.

Symptoms of leaf roll, swollen nodes, flat branch and witches' broom were observed in five cultivars of sweet cherry from Srinagar, Jammu and Kashmir province, India, during 2019-2021. Phytoplasmas association were confirmed by amplifying 16S rRNA, secA, rp, tuf and secY genes with phytoplasma-specific primers in all symptomatic sweet cherry cultivars in nested PCR assays. Pairwise sequence comparison, phylogeny and virtual RFLP (16S rRNA gene) analyses confirmed the presence of 'Candidatus Phytoplasma asteris' and 'Ca. P. trifolii' strains in the sweet cherry samples. The incidence of flat branch and witches' broom symptoms associated with 'Ca. P. trifolii' varied from 5.8 to 25% in cultivars Bigarreau Nepoleon (Double), Bigarreau Noir Grossa and CITH-Cherry-9. However, incidence of leaf rolling, swollen nodes and bud proliferation associated with 'Ca. P. asteris' was recorded 7.5% in cultivar Stella and 10% in Sunburst, respectively, in the surveyed area. The multigene characterization of sweet cherry phytoplasma strains confirmed the validity of these molecular markers for identification of phytoplasmas enclosed in 16SrI and 16SrVI groups. The presence of phytoplasmas in sweet cherry is the first report from India.

Carbon dots decorated cadmium sulphide heterojunction-nanospheres for the enhanced visible light driven photocatalytic dye degradation and hydrogen generation.

Carbon dots (C-dots) developed from beetroot is used for the rational design of cadmium sulphide based heterojunction photocatalysts (C-dots@CdS) using hydrothermal technique. The crystal structure, phase, morphology and optical characteristics of the synthesised materials are determined using X-ray diffraction (XRD), High resolution transmission electron microscopy (HR-TEM), Field emission scanning electron microscopy (FESEM), Energy dispersive X-ray analysis (EDAX), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, UV-Visible diffuse reflectance spectroscopy (UV-DRS), photoluminescence spectroscopy (PL spectroscopy), BET adsorption, X-ray photoelectron spectroscopy (XPS) and electrochemical studies. Using C-dots@CdS catalytic system, a superior photocatalytic activity relative to the undecorated CdS is observed. Among the C-dots@CdS samples, the CdS loaded with 6 wt% of C-dots exhibited enhanced hydrogen evolution rate compared with other samples considered for the study. CdS nanospheres modified with C-dots (6 wt%) resulted in the photocatalytic hydrogen evolution rate of 1582 µmolg-1 against 849 µmolg-1 evolution rate obtained for CdS nanospheres within 3 h. In spite of being 0D/0D type nano-heteroarchitecture, C-dots@CdS system obtained an apparent quantum yield of 6.37 % for the catalytic dosage of 20 mg under the irradiation of visible light. CdS in the C-dots@CdS system serves as the light harvester while C-dots with discernible edges can maintain the continuous supply of photo-excited charge carriers and hence can reduce the charge-carrier recombination. Further, the photodegradation of crystal violet dye using the optimised dosage of C-dots@CdS-6 exhibited an efficiency of 97.3 % in 120 min of visible light irradiation under neutral conditions. The detailed kinetic study reveals that the mechanism of photodegradation of crystal violet dye using C-dots@CdS system can be described using pseudo-second-order kinetics. The presence of oxygen rich hydrophilic surface functionalities of C-dots, the formation of near-surface heterojunction and the suitable band structure of C-dots@CdS system leading to the optimum charge carrier separation kinetics can be attributed to the enhanced photocatalytic performance. This work offers a promising strategy to develop bio-derived C-dots based heterojunction photocatalyst to address the burgeoning energy and environmental demands.

Development of multiplex RT-PCR assay for simultaneous detection of four viruses infecting apple (Malus domestica).

The major viruses infecting apple cultivars throughout the world including India are apple mosaic virus (ApMV), apple stem pitting virus (ASPV), apple stem grooving virus (ASGV), apple chlorotic leaf spot virus (ACLSV), and recently, a new virus, apple necrotic mosaic virus (ApNMV), was reported from mosaic-infected apple cultivars in India. The aim of this study was to detect the ApNMV virus along with the other three viruses (ApMV, ASPV and ASGV) simultaneously by multiplex RT-PCR. Four primer-pair-produced amplicons of 670, 550, 350 and 210 bp corresponding to ApNMV, ApMV, ASPV and ASGV, respectively, were found to be specific for these viruses when tested individually. The annealing temperature (55°C), primer concentration (0·8 µl) and other components of the master mix were standardized for the development of one-step m-RT-PCR assay. The m-RT-PCR protocol developed was further validated with 30 samples from seven symptomatic or asymptomatic apple cultivars, which revealed the presence of more than one virus in these cultivars. Most of the viruses were found to be present either alone or in mixed infection; however, ASPV was more common in tested cultivars. An easy, cost-effective and rapid multiplex RT-RCR protocol was developed to detect the four viruses, which infect apple plants either in individually or together in the field. This assay will help in the surveying and indexing of apple germplasm and the distribution of all four viruses in the apple growing regions of India.

A path model approach to safety compliance and personal factors among electrical workers in India.

This article reports the findings from a safety research survey conducted among the employees of a large public-sector electrical utility in the state of Kerala, India. Responses from 3017 employees were collected by one-to-one interaction using the developed instrument. Personal factors like self-esteem, job stress, personal stress, social support and fatigue of the targeted population were measured. Personal safety climate factors of the utility were accessed by modifying the existing safety climate scales. Statistical analysis confirmed the reliability and validity of the factors in the study. A significant path model of personal and safety climate factors was developed. Seven research hypotheses were validated using statistical analysis. The results of the study highlighted the need for safety participation, safety knowledge, safety training and interventions to reduce personal issues in the workplace. These findings provide valuable insights for safety professionals for implementing novel methods to ensure workplace safety.

Nonapoptotic role of caspase-3 in regulating Rho1GTPase-mediated morphogenesis of epithelial tubes of Drosophila renal system.

BACKGROUND: Cells trigger caspase-mediated apoptosis to eliminate themselves from the system when tissue needs to be sculptured, or they detect any abnormality within them, thus preventing irreparable damage to the host. However, nonapoptotic activities of caspases are also involved in many cellular functions. Interestingly, Drosophila Malpighian tubules (MTs) express apoptotic proteins, without succumbing to cell death. RESULTS: We show apoptosis-independent role of executioner caspase-3, Drice, in MT morphogenesis. Drice is required for precise cytoskeleton organization and convergent extension, failing which morphology, size, cell number, and arrangement get affected. Furthermore, characteristic stellate cell shape transformation in MTs is also governed by Drice. Genetic interaction study shows that Drice mediates its action by regulating Rho1GTPase functionally, and localization of polarity protein Disc large. Subsequently, downregulation of Rho1GTPase in Drice mutants significantly rescues the cystic MTs phenotype. The study shows a mechanism by which Drice governs tubulogenesis via Rho1GTPase-mediated coordinated organization of actin cytoskeleton and membrane stabilization. CONCLUSION: Collectively our findings suggest a nonapoptotic function of caspase-3 in fine-tuning of cellular rearrangement during tubule development, and these results will add to the growing understanding of diverse roles of caspases during its evolution in metazoans.

Extreme Lengthening of Tibia Using Bone Transport Technique: A Rare Case Report.

This is a case describing a 13-year-old female student having a history of a fall-developed wound over the anterior aspect of the right leg with discharging sinus treated as chronic osteomyelitis and operated and distal tibia corticotomy and Ilizarov fixation was done. The patient was full of complications, but full limb lengthening was restored with follow-up. The Ilizarov frame's proper installation and the middle segment's efficient transportation are essential variables in reducing the likelihood of the transported segment deviating.

Tumescent Local Anesthesia in Parotid Abscess - Novel Application of Old Technique.

Tumescent local anesthesia (TLA) is a regional anesthetic technique in which the diluted local anesthetic drug (commonly lidocaine) and epinephrine solution in large volume is injected subcutaneously around the site of incision. The main advantages of TLA are excellent bloodless field and longer duration of analgesia because of addition of epinephrine. Although TLA was used in various surgical procedures, there is no literature to date that has reported its use in the parotid region. Hence, we present an interesting case where this old technique found a novel application in avoiding general anesthesia and its sequelae. We also believe that it provides valuable information to doctors of various categories such as surgeons, Anesthesiologists and general practitioners/family physicians.

Transcriptome profiling identifies multistep regulation through E93, Forkhead and Ecdysone Oxidase in survival of Malpighian tubules during metamorphosis in Drosophila.

Drosophila metamorphosis is associated with substantial metabolic activity involving cell death and cell proliferation leading to differentiation of adult tissues and structures. Unlike other larval tissues, Malpighian tubules (MTs) exhibit apoptotic immunity and do not undergo cell death but are carried over to the adult with some cell reorganisation. They persist despite the fact that they express apoptotic proteins and caspases. In the present study, we analysed the global transcription changes in MTs and compared with salivary glands, to decipher the biology of MTs. Gene set enrichment analysis indicated reduced expression of many ecdysone induced genes, including the critical regulator of cell death, E93 in MTs. We hypothesize that reduction of E93 could be because of over expression of ecdysone oxidase, which is high in MTs and is responsible for regulation of hormone titer by degradation of ecdysone. Ectopic expression of E93 in MTs results in cell death through autophagy. Fork head, which is crucial for survival, is enriched in the MT transcriptome, and its down regulation in MTs could be consequent to over expression of E93. Together our data suggests that the cascade of events initiated by ecdysone mediates survival of MTs through concerted action of multiple factors.

SLC1A3 C3590T but not BDNF G196A is a predisposition factor for stress as well as depression, in an adolescent eastern Indian population.

BACKGROUND: Adolescence is a distinctive stage of various changes and is noted as peak age for onset of many psychiatric disorders, especially linked to stress and depression. Several genetic variations are being increasingly known to be linked with stress and depression. The polymorphisms in two such genes, the BDNF and SLC1A3, have been reported to be linked with either depression/stress or with suicidal behaviour. These genes have not been validated in Indian population, and therefore there is a need to investigate these genes in Indian population. The present study was undertaken to test whether the known polymorphisms SLC1A3 C3590T, SLC1A3 C869G and BDNF G196A are associated or not with stress or depression in an eastern Indian population. METHODS: A case-control association study was performed with 108 cases having variable levels of stress and depression and 205 matched controls. Detection of stress and depression was done by using standard instruments as PSS and CES-D, respectively and demographic profile was obtained for each individual on the basis of personal data sheet. Genotyping for the selected polymorphisms was performed by PCR followed by restriction digestion. RESULTS: The SNP SLC1A3 C3590T was found to be associated with stress and depression (p = 0.0042, OR = 2.072). Therefore, the T allele increases the risk by more than two folds for stress and depression in the present population. The other allele of SLC1A3, G869C, as well as BDNF G196A were not associated with stress or depression in the population studied. CONCLUSION: SLC1A3 C3590T is a predisposition factor for stress and depression in an eastern Indian population, whereas SLC1A3 G869C and BDNF G196A were not found to be a risk factor. Therefore, presence of T allele of SLC1A3 C3590T, may predict the development of stress and depression in an individual. This may also help in the understanding of pathophysiology of the disease. However, these findings warrant a wider study in Indian populations and would be of significance in understanding the predisposition of stress and depression in this population.

Correction to: Molecular basis for efficacy of Guduchi and Madhuyashti feeding on different environmental stressors in Drosophila.

It has come to authors' attention that an inadvertent mistake was made in the construction of Figure 4 and Figure 6 of the original publication.

Molecular basis for efficacy of Guduchi and Madhuyashti feeding on different environmental stressors in Drosophila.

Stressors of different kinds adversely affect life history parameters like growth, development, and reproduction. Organisms overcome the negative impact of environmental stressors and strive to reach a tolerant state through genetic and metabolic activities. Ayurvedic formulations are reported to have life trait benefitting properties which improve capacity to withstand stress and tolerate adverse conditions. Guduchi (Tinospora cordifolia) and Madhuyashti (Glycirrhiza glabra) Ayurvedic formulations are known to have immunomodulatory, intellect promoting, and adaptogenic properties, thus favoring good health and healthy aging. Present study investigates the efficacy of Guduchi and Madhuyashti in providing tolerance to different stresses and the underlying mechanisms using the Drosophila model. Drosophila larvae/flies fed on Guduchi or Madhuyashti were better thermo-protected, which correlated with increased expression of heat shock genes even without the heat shock. Guduchi or Madhuyashti feeding also increased antimicrobial peptide expression, thus providing better tolerance to pathogenic assaults. Feeding on Guduchi- or Madhuyashti- supplemented food also enhanced starvation and desiccation tolerance. However, neither of these formulations provided beneficial effects when grown under crowded conditions or when exposed to oxidative stressors.

Complex effects of Ayurvedic formulation: Guduchi and Madhuyashti on different components of life history may elude the elixir effect.

Formulations from the traditional Indian medicine, Ayurveda, have long been considered to have potent life-style enhancing effects, possibly by their effect(s) on key life-history attributes. Although several studies have reported beneficial effects of these formulations on different components of life history, few have investigated their concurrent influence on various life-history traits. Here, we report the results of an investigation showing the effect of two well-known Ayurvedic formulations, Guduchi and Madhuyashti, on fecundity and longevity of Drosophila melanogaster. Flies were either grown (i.e., larval exposure) and/or maintained (i.e., adult exposure) on standard food supplemented with 0.5% Guduchi or 0.5% Madhuyashti. It was observed that the longevity of adult flies of both sexes was not affected on feeding Guduchifood, but fecundity of the females was greatly enhanced. Fecundity was also found to be affected by the adult food and whether their mates were grown on Guduchi or normal food. Madhuyashti, on the other hand, significantly reduced mean longevity and had a stimulatory effect on female fecundity. This fecundity enhancing effect however seemed to be mediated through its effect on the males. Interestingly, much of these effects interacted with age in a complex way, making it difficult to generalize the overall effect of these formulations on the reproductive output of the flies. Ourstudy underlines the importance of evaluating the interacting effects of these (and similar) formulations on a range of life-history traits in a holistic way to understand their utility better.

Yorkie Regulates Neurodegeneration Through Canonical Pathway and Innate Immune Response.

Expansion of CAG repeats in certain genes has long been known to be associated with neurodegenerastion, but the quest to identity the underlying mechanisms is still on. Here, we analyzed the role of Yorkie, the coactivator of the Hippo pathway, and provide evidence to state that it is a robust genetic modifier of polyglutamine (PolyQ)-mediated neurodegeneration. Yorkie reduces the pathogenicity of inclusion bodies in the cell by activating cyclin E and bantam, rather than by preventing apoptosis through DIAP1. PolyQ aggregates inhibit Yorkie functioning at the protein, rather than the transcript level, and this is probably accomplished by the interaction between PolyQ and Yorkie. We show that PolyQ aggregates upregulate expression of antimicrobial peptides (AMPs) and Yorkie negatively regulates immune deficiency (IMD) and Toll pathways through relish and cactus, respectively, thus reducing AMPs and mitigating PolyQ affects. These studies strongly suggest a novel mechanism of suppression of PolyQ-mediated neurotoxicity by Yorkie through multiple channels.