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Tomato (Solanum lycopersicumL.) is an important and widely grown vegetable crop throughout India, and it has been attacked by several insect pests. This study sheds light on the infestation of Mylabris pustulatasince its damage is noticed on tomato crop by feeding on buds, flowers, fruits, and sometimes even on tender leaves of tomato, either solitarily or gregariously. Further, the morphological and molecular identification (accession number-OP647113.1) carried out also confirms M. pustulataas a feeding agent. This is the new report on tomato crop infested by blister beetle, M. pustulata,observed in Lakhamandal village of Dehradun, Uttarakhand, India.

Transcranial direct current stimulation (tDCS) is an effective and safe noninvasive brain stimulation (NIBS) procedure to modulate neuronal excitability. The present preclinical study was carried out to validate the impact of the innovative high definition (HD) fabricated spiking Au/AgCl electrodes via a noninvasive tDCS procedure on a rat model with depression-like behavior. In this study, a chronic stress-induced depression-like behavior rat model was developed over a period of 14 days. Furthermore, the aftereffects of NIBS procedures were investigated by providing a tDCS dose ( ${2.00} \text {mA} \times {5.00} \text {min}$ ) by placing the electrodes on the interested region of the rat brain. This study was performed in healthy rats, control rats with depression-like behavior, and tDCS treated rats, which were used to examine the differential aftereffects of tDCS dose. After single tDCS dose, a significant increase in average band power of electroencephalogram (EEG) has been observed ( $\text {F}{(}{2},{15}{)} = {8.376}; {P} = {0.0036}$ ) alongside a significant increase in the glutamate level of hippocampus (HPC; $\text {F}{(}{2},\!{15}{)} = {8.919}; {P} = {0.0028}$ ), a significant reduction in immobility time ( $\text {F}{(}{2},{15}{)} = {7.552}; {P} = {0.0054}$ ), and a significant increase in the percentage sucrose intake has been observed ( $\text {F}{(}{2}, {15}{)} = {5.941}; {P} = {0.0126}$ ). In addition, immunohistochemistry (IHC) showed a significant increase in the Iba1 protein expression in microglia cell in the both cortex and HPC region ( ${P} < {0.05}$ ). Hence, the fabricated electrodes can deliver a tDCS dose that can penetrate up to the cortex and HPC regions from the surface of brain noninvasively within tolerable and safety limits.

Dual leucine zipper kinase (DLK) and leucine zipper-bearing kinase (LZK) are regulators of neuronal degeneration and axon growth. Therefore, there is a considerable interest in developing DLK/LZK inhibitors for neurodegenerative diseases. Herein, we use ligand- and structure-based drug design approaches for identifying novel amino-pyrazine inhibitors of DLK/LZK. DN-1289 (14), a potent and selective dual DLK/LZK inhibitor, demonstrated excellent in vivo plasma half-life across species and is anticipated to freely penetrate the central nervous system with no brain impairment based on in vivo rodent pharmacokinetic studies and human in vitro transporter data. Proximal target engagement and disease relevant pathway biomarkers were also favorably regulated in an in vivo model of amyotrophic lateral sclerosis.

Human genetic data indicate that microglial dysfunction contributes to the pathology of Alzheimer’s disease (AD), exemplified by the identification of coding variants in triggering receptor expressed on myeloid cells 2 (TREM2) and, more recently, in PLCG2, a phospholipase-encoding gene expressed in microglia. Although studies in mouse models have implicated specific Trem2-dependent microglial functions in AD, the underlying molecular mechanisms and translatability to human disease remain poorly defined. In this study, we used genetically engineered human induced pluripotent stem cell-derived microglia-like cells to show that TREM2 signals through PLCγ2 to mediate cell survival, phagocytosis, processing of neuronal debris, and lipid metabolism. Loss of TREM2 or PLCγ2 signaling leads to a shared signature of transcriptional dysregulation that underlies these phenotypes. Independent of TREM2, PLCγ2 also signals downstream of Toll-like receptors to mediate inflammatory responses. Therefore, PLCγ2 activity regulates divergent microglial functions via distinct TREM2-dependent and -independent signaling and might be involved in the transition to a microglial state associated with neurodegenerative disease.

All mechanical components suffer from monotonically increasing wear/deterioration. A non-stationary gamma wear process can model such a wear by taking care of the temporal variability in the wear phenomenon; however, this makes the shape parameter of the gamma process a function of time leading to a problem in its simulation, especially so in the presence of other competing failure modes. This paper presents a method by which one can map a non-stationary gamma wear process to a mixed exponential process and demonstrate its suitability for analysis through a simulation package involving use of stochastic petrinets. A stochastic petrinet simulation package 'Timenet' compares the result of the above method with the analytically determined result through a Matlab program. The originality of the paper lies in demonstration of a method for analysis of a non-stationary gamma wear process through a simulation package.

Alterations in the composition of the intestinal microbiota have been correlated with aging and measures of frailty in the elderly. However, the relationships between microbial dynamics, age-related changes in intestinal physiology, and organismal health remain poorly understood. Here, we show that dysbiosis of the intestinal microbiota, characterized by an expansion of the Gammaproteobacteria, is tightly linked to age-onset intestinal barrier dysfunction in Drosophila. Indeed, alterations in the microbiota precede and predict the onset of intestinal barrier dysfunction in aged flies. Changes in microbial composition occurring prior to intestinal barrier dysfunction contribute to changes in excretory function and immune gene activation in the aging intestine. In addition, we show that a distinct shift in microbiota composition follows intestinal barrier dysfunction, leading to systemic immune activation and organismal death. Our results indicate that alterations in microbiota dynamics could contribute to and also predict varying rates of health decline during aging in mammals.

AMPK exerts prolongevity effects in diverse species; however, the tissue-specific mechanisms involved are poorly understood. Here, we show that upregulation of AMPK in the adult Drosophilanervous system induces autophagy both in the brain and also in the intestinal epithelium. Induction of autophagy is linked to improved intestinal homeostasis during aging and extended lifespan. Neuronal upregulation of the autophagy-specific protein kinase Atg1 is both necessary and sufficient to induce these intertissue effects during aging and to prolong the lifespan. Furthermore, upregulation of AMPK in the adult intestine induces autophagy both cell autonomously and non-cell-autonomously in the brain, slows systemic aging, and prolongs the lifespan. We show that the organism-wide response to tissue-specific AMPK/Atg1 activation is linked to reduced insulin-like peptide levels in the brain and a systemic increase in 4E-BP expression. Together, these results reveal that localized activation of AMPK and/or Atg1 in key tissues can slow aging in a non-cell-autonomous manner.

Hydroxyurea, a well-known DNA replication inhibitor, induces cell cycle arrest and intact checkpoint functions are required to survive DNA replication stress induced by this genotoxic agent. Perturbed DNA synthesis also results in elevated levels of DNA damage. It is unclear how organisms prevent accumulation of this type of DNA damage that coincides with hampered DNA synthesis. Here, we report the identification of stonewall (stwl)as a novel hydroxyurea-hypersensitive mutant. We demonstrate that Stwl is required to prevent accumulation of DNA damage induced by hydroxyurea; yet, Stwl is not involved in S/M checkpoint regulation. We show that Stwl is a heterochromatin-associated protein with transcription-repressing capacities. In stwl mutants, levels of trimethylated H3K27 and H3K9 (two hallmarks of silent chromatin) are decreased. Our data provide evidence for a Stwl-dependent epigenetic mechanism that is involved in the maintenance of the normal balance between euchromatin and heterochromatin and that is required to prevent accumulation of DNA damage in the presence of DNA replication stress.

Hydroxyurea, a well-known DNA replication inhibitor, induces cell cycle arrest and intact checkpoint functions are required to survive DNA replication stress induced by this genotoxic agent. Perturbed DNA synthesis also results in elevated levels of DNA damage. It is unclear how organisms prevent accumulation of this type of DNA damage that coincides with hampered DNA synthesis. Here, we report the identification of stonewall (stwl) as a novel hydroxyurea-hypersensitive mutant. We demonstrate that Stwl is required to prevent accumulation of DNA damage induced by hydroxyurea; yet, Stwl is not involved in S/M checkpoint regulation. We show that Stwl is a heterochromatin-associated protein with transcription-repressing capacities. In stwl mutants, levels of trimethylated H3K27 and H3K9 (two hallmarks of silent chromatin) are decreased. Our data provide evidence for a Stwl-dependent epigenetic mechanism that is involved in the maintenance of the normal balance between euchromatin and heterochromatin and that is required to prevent accumulation of DNA damage in the presence of DNA replication stress.

Glycogen synthase kinase-3 (Gsk-3β) aberration act as a crucial pathogenic factor in several neurological conditions. However its role in menopause associated behavioural impairments is still not unclear. The present study was designed to understand the role of Gsk-3β in the progression of neurobehavioural impairments in middle-aged ovariectomized (ovx) rats. The animals showed a significant impairment in spatial and recognition memory, along with anxiety and depression-like behaviour following 22 weeks of ovx. The genomic expression of ERα, ERβ, Nrf2, HO-1, TNFα, and IL-6was altered in both the cortex and the hippocampus of ovx rats. Protein expression of p-Gsk-3β(Ser9) was significantly downregulated in the cortex after ovx. However, the hippocampus showed a surprisingly opposite trend in the levels of p-Gsk-3β(Ser9) as that of the cortex. Differential activation of Gsk-3β and its downstream proteins such as β-catenin and p-mTOR were also altered following ovx. The study concluded that differential activation of Gsk-3β, along with oxidative stress and neuroinflammation in the cortex and the hippocampus, leads to the induction of cognitive and behaviour impairments in ovx rats.

A rare case of gallbladder duplication, an unusual biliary anomaly is reported in a young female patient presenting with acute cholecystitis. After a confirmed diagnosis of double gallbladder was made by sonography, endoscopic retrograde cholangio-pancreaticography (ERCP), and magnetic retrograde cholangio-pancreaticography(MRCP), both gallbladders were removed laparoscopically. On histology both gallbladders showed cholesterolosis. Detailed preoperative investigations are required for an accurate preoperative diagnosis before considering laparoscopic cholecystectomy to avoid inadvertent damage to biliary ductal system and overlooking of second gallbladder during surgery.