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Induction of tetraploidy in citrus is aimed for the development of triploid seedless cultivars, which are needed for meeting the requirements of the citrus industry. The present study was carried out during 2020 and 2021 at ICAR-Indian Agricultural Research Institute, New Delhi to identify suitable tetraploids in vegetatively propagated second generation of the colchiploids in sweet orange [Citrus sinensis (L.) Osbeck] cv. Mosambi. The 3-year-old, 20 2nd generation colchicine treated (0.05, 0.10, 0.15 and 0.20%) plants, developed from the putative tetraploid branches of the first generation colchiploids of sweet orange cv. Mosambi, budded on Jatti khatti rootstock along with their wild (parent) type, were characterized based on morphological and physiological traits. Leaf area, fresh weight and succulency increased, but density of foliar tissue and leaf dry weight reduced in majority of the colchiploids. Leaf length, width and thickness also increased in colchiploids in comparison to their wild type. Fruit weight, length, width and rind thickness also increased in the colchiploids in comparison to their wild type. Juice TSS reduced, but acidity increased in majority of these Mosambi colchiploids. Seed number was lowest in M-3 (7.33) colchiploid. Total carotenoids and chlorophyll fractions also increased in majority of the colchiploids. On the basis of morpho-physio-biochemical trait characterization, 8 solid tetraploids (M-1, M-3, M-2, M-5, M-4, M-7, M-13 and M-16) of Mosambi were identified, which can be used in future breeding programmes for the development of seedless triploids of Mosambi.

Nitrogen (N) is one of the primary macronutrients required for crop growth and yield. This nutrient is especially limiting wheat yields in the dry and low fertile agro-ecologies having low N in the root zone soil strata. Moreover, majority of farmers in India and South Asia are small to marginal with meagre capacity to invest in costly nitrogen fertilizers. Therefore, there is an immense need to identify lines that use nitrogen efficiently. A set of 50 diverse wheat genotypes consisting of indigenous germplasm lines (05), cultivars released for commercial cultivation (23) and selected elite lines from CIMMYT nurseries (22) were evaluated in an alpha-lattice design with two replications, a six-rowed plot of 2.5m length for 24 agro morphological, physiological and NUE related traits during two consecutive crop seasons in an N-depleted precision field under two different N levels of 50%-N50 (T1) and 100%-N100 (T2) of recommended N, i.e., 100 kg/ha. Analysis of variance revealed significant genetic variation among genotypes for all the traits studied. About 11.36% yield reduction was observed at reduced N levels. Significant correlations among NUE traits and yield component traits were observed which indicated pivotal role of N remobilization to the grain in enhancing yield levels. Among N-insensitive genotypes identified based on their yielding ability at low N levels, UASBW13356, UASBW13358, UASBW13354, UASBW13357 and KRL1-4 showed their inherent genotypic plasticity toward N application. The genotypes with more yield and high to moderate NUtE can be used as parents for the breeding of N efficient genotypes for marginal agro-ecologies. Low N tolerant genotypes identified from the current investigation may be further utilized in the identification of genomic regions responsible for NUE and its deployment in wheat breeding programs. The comprehensive data of 24 traits under different nitrogen levels for diverse genotypes from India and global sources (mainly CIMMYT) should be useful for supporting breeding for NUE and thus will be of great help for small and marginal farmers in India and South Asia.

The present experiment aimed to establish the efficacy of dietary inclusion of a novel feed supplement on plane of nutrition, milk yield, and its characteristics, reproductive events and circulating concentrations of reproductive hormones in dairy cows during early lactation. Twelve post-partum crossbred lactating cows were equally and randomly assigned to two dietary treatments for 90 days. The cows in CON (control) group were fed on green fodder and wheat straw-based diet with concentrate mixture, whereas, cows in NFS (Novel Feed Supplement) group were fed according to CON group with additional novel feed supplement @0.25% of BW. A comparative study of plane of nutrition revealed that both DCP and TDN were deficient in CON by 12.0 and 18.99%, respectively, however, it was sufficient in NFS group. The daily and total milk yield (kg), 4% FCM, ECM, fat and protein yields (g/d) were improved in NFS than CON group. The average composition of milk showed no significant difference throughout the study. The supplement fed cows had an evident early return of heat (26.20 d in NFS v/s 42.60 d in CON) with enhanced conception rate (66.7% in NFS v/s 50% in CON). The estradiol concentration (pg/ml) was reduced and progesterone concentration (ng/ml) was enhanced in NFS fed cows. In conclusion, incorporation of the novel feed supplement @0.25% of BW significantly improved the plane of nutrition, milk production and reproduction in lactating crossbred cows during the early post-partum period.

The present study was carried out in the Mango orchards at Indian Agricultural Research Institute, New Delhi during 2020–2021 and 2021–2022 and aimed at analysing the population dynamics of fruit fly (Bactrocera dorsalis) species after putting the requisite number of methyl eugenol traps (@6 per acre). Weekly monitoring of fruit fly populations was performed and correlated with various weather parameters. Among the fruit fly species, the oriental fruit fly was found to be the most prevalent and abundant, followed by B. zonata, B. correcta, and B. cucurbitae. Fruit fly populations peaked in mango plantations between June and July, coinciding with the ripening time and the occurrence of humid conditions and rainfall. Multiple factors, including weather conditions, the presence of preferred host plants, and alternative hosts, fruits characteristics were found to influence the dynamics of fruit fly populations. The seasonal trap captures of male fruit flies showed a moderately significant negative correlation (-0.612*) with maximum but significant positive correlation with the minimum temperature (0.701**). However, a positive correlation was observed between relative humidity (r = 0.924**) and rainfall (r = 0.721**) with the fluctuations of fruit fly populations across all the monitored orchard sites.

An experiment was conducted during 2018–21 at the research farms of Kittur Rani Channamma College of Horticulture (University of Horticultural Sciences, Bagalkot, Karnataka), Arabhavi, Karnataka to study the effect of post-shooting sprays of nutrients for improving fruit quality, antioxidant properties and shelf-life in banana (Musa sp.). Effects of potassium sulphate (SOP) @20 g/L and micro-nutrients, viz. customised micronutrient mix Arka Banana SpecialTM @5 g/L, zinc sulphate @1 g/L, boric acid @ 2 g/L, ferrous sulphate- EDTA @3 g/L and copper sulphate @2 g/L sprays in different combinations imposed at post-shooting stage were evaluated in terms of fruit quality and shelf-life after ripening in banana cv. Grand Naine. Treatment comprising of SOP @20 g/L and Arka Banana SpecialTM @5 g/L improved pulp TSS (22.300B), TSS: TA ratio (71.26), fruit firmness (5.16 lb), MSI (18.12%) and peroxidase (POD) activity (15.98ΔA470/min/g). While polyphenol oxidase (PPO) activity (120.42 U/ mg protein), peel browning index (1.42), fruit weight loss (12.73%) and titratable acidity (0.31%) were declined. An increase in green life (8.22 days) and yellow life (3.93 days) of fruits by potassium application, enhancing the storage and shelf-life of the fruits. Pulp TSS was positively correlated with total sugars (0.938**), TSS: acid ratio (0.981**), shelf-life (0.955**), fruit firmness (0.931**) and MSI (0.921**), and negatively correlated with TA (-0.980**) and PPO activity (-0.967**).

Background Oncolytic viruses are considered part of immunotherapy and have shown promise in preclinical experiments and clinical trials. Results from these studies have suggested that tumor microenvironment remodeling is required to achieve an effective response in solid tumors. Here, we assess the extent to which targeting specific mechanisms underlying the immunosuppressive tumor microenvironment optimizes viroimmunotherapy.Methods We used RNA-seq analyses to analyze the transcriptome, and validated the results using Q-PCR, flow cytometry, and immunofluorescence. Viral activity was analyzed by replication assays and viral titration. Kyn and Trp metabolite levels were quantified using liquid chromatography–mass spectrometry. Aryl hydrocarbon receptor (AhR) activation was analyzed by examination of promoter activity. Therapeutic efficacy was assessed by tumor histopathology and survival in syngeneic murine models of gliomas, including Indoleamine 2,3-dioxygenase (IDO)-/- mice. Flow cytometry was used for immunophenotyping and quantification of cell populations. Immune activation was examined in co-cultures of immune and cancer cells. T-cell depletion was used to identify the role played by specific cell populations. Rechallenge experiments were performed to identify the development of anti-tumor memory.Results Bulk RNA-seq analyses showed the activation of the immunosuppressive IDO-kynurenine-AhR circuitry in response to Delta-24-RGDOX infection of tumors. To overcome the effect of this pivotal pathway, we combined Delta-24-RGDOX with clinically relevant IDO inhibitors. The combination therapy increased the frequency of CD8+ T cells and decreased the rate of myeloid-derived suppressor cell and immunosupressive Treg tumor populations in animal models of solid tumors. Functional studies demonstrated that IDO-blockade-dependent activation of immune cells against tumor antigens could be reversed by the oncometabolite kynurenine. The concurrent targeting of the effectors and suppressors of the tumor immune landscape significantly prolonged the survival in animal models of orthotopic gliomas.Conclusions Our data identified for the first time the in vivo role of IDO-dependent immunosuppressive pathways in the resistance of solid tumors to oncolytic adenoviruses. Specifically, the IDO-Kyn-AhR activity was responsible for the resurface of local immunosuppression and resistance to therapy, which was ablated through IDO inhibition. Our data indicate that combined molecular and immune therapy may improve outcomes in human gliomas and other cancers treated with virotherapy.

The present study was carried to identify polymorphic SSRs derived from the whole draft genome data of mango (Mangifera indica L.) for their polymorphism between Amrapali and Sensation genotypes (parents) and their validation on the derived hybrid progenies. Fifty new hypervariable mango SSRs (HMSSRs) were screened against the parental genotypes. Out of which, 11 HMSSRs were polymorphic, 18 were monomorphic and 21 did not amplify at all. These polymorphic HMSSRs were then used for ascertaining the hybridity of the hybrid progenies. The genetic diversity indices of each SSR locus among mango hybrids were calculated using Power Marker ver. 3.25. The genetic diversity indices such as the number of alleles ranged from 2 (HMSSR35) to 5 (HMSSR57), gene diversity from 0.36 (HMSSR54) to 0.71 (HMSSR57 & HMSSR58), and PIC values from 0.35 (HMSSR69) to 0.66 (HMSSR57). The dendrogram generated using Neighbor joining tree divided the 22 genotypes into three distinct clades, viz. Clade ‘A’, Clade ‘B’ and Clade ‘C’. The hybrids, viz. H-3-1, H-3-2, and H-7-4 were identified as true hybrids, since they were genetically more close to female parent (Amrapali), while hybrids H-3-3, H-3-11, H-11-1, H-12-5, H-1-6, H-1-13, H-12-8, H-12-10, H-3-12, H-1-1 and H-4-10 were more close to the male donor parent (Sensation) and also had red peel colour. In the present study, the 20 hybrids were confirmed to be the true hybrids since the bands unique to the two parents were present in them.

The term Rhupus is coded for the individuals who have rheumatoid like arthritis with erosions and fulfil the criteria for both rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Abnormal Th2 cell plays a central role in SLE while Th1 participate in RA. Thus the overlap of SLE and RA has a very low incidence (0.01%-0.2%) in patient with arthritis. This 40-year-old male patient presented with complains of severe multiple joint pain with progressive deformities, diminished vision from last 2 months, redness on back, headache and swelling over scalp. As this patient had history of severe trauma that was considered as a precipitating factor for ongoing chronic inflammatory disorder. Posterior subcapsular cataract was explained by prolong use of systemic steroid and rashes on the lower back due to sulfasalazine. Radioimaging study revealed arachnoid cyst and calcified projection arising from outer table of skull, which was kept under observation.

In the present study 30 gladiolus genotypes were evaluated for different traits and reaction to two virulent strains of Fusarium, viz. IARI isolate (F. oxysporum f. sp. gladioli – Fog isolate 1) and Pantnagar isolate (F. oxysporum f. sp. gladioli - Fog isolate 2). The two healthy uniform sized corms were planted in individual pots (12â€) filled with potting mixture (soil: FYM: sand; 2:1:1) in five replications. Before planting, the corms were treated with suspension of Fusarium (3 × 106/ml) for 24 hr. Among the genotypes, Dhanwantri (14.59%), Pusa Unnati (14.59%), Swarnima (16.54%), and hybrid Smokey Lady × Oscar (22.92%) were found tolerant to both the Fusarium isolates. The maximum plant height, spike length, rachis length and mean number of florets/spike were noted in Pusa Unnati, but the earliest spike emergence took place in Jyotsana (87.37 days), earliest opening of first floret was noted in Melody (103.79 days). The maximum mean corm weight (87.58 g) was noted in Jyotsana, while maximum diameter was found in Dhanwantri (6.56 cm). Leaves and corms were sampled at 60 days of planting for estimation of different biochemical parameters, viz., total chlorophyll, total phenol, malondialdehyde (MDA) content and H2O2 peroxidation. The tolerant genotypes had higher levels of leaf total chlorophylls and total phenols. The H2O2 evolution and malondialdehyde (MDA) content showed marked increment due to in vivo inoculation of the pathogen. Correlation studies with plant mortality index (PMI) showed a positive correlation for DSI (0.899), while negative correlations were estimated for MDA content (0.879**) followed by H2O2 formation (0.862**), total phenol (r = 0.810**) and total chlorophyll (r = -0.754**). Results showed that genotypes, namely, Dhanwantri, Pusa Unnati, Swarnima, and hybrid Smokey Lady × Oscar were Fusarium wilt tolerant along with desirable agronomic traits, thus can be recommended for commercial cultivation.

Rapeseed (Brassica napus) is an important oil seed crop, providing more than 13% of the world’s supply of edible oils. An in-depth knowledge of the gene network involved in biosynthesis and accumulation of seed oil is critical for the improvement of B. napus. Using available genomic and transcriptomic resources, we identified 1,750 acyl lipid metabolism (ALM) genes that are distributed over 19 chromosomes in the B. napus genome. B. rapa and B. oleracea, two diploid progenitors of B. napus, contributed almost equally to the ALM genes. Genome collinearity analysis demonstrated that the majority of the ALM genes have arisen due to genome duplication or segmental duplication events. In addition, we profiled the expression patterns of the ALM genes in four different developmental stages. Furthermore, we developed two B. napus near isogenic lines (NILs). The high oil NIL, YC13-559, accumulates more than 10% of seed oil compared to the other, YC13-554. Comparative gene expression analysis revealed upregulation of lipid biosynthesis-related regulatory genes in YC13-559, including SHOOTMERISTEMLESS, LEAFY COTYLEDON 1 (LEC1), LEC2, FUSCA3, ABSCISIC ACID INSENSITIVE 3 (ABI3), ABI4, ABI5, and WRINKLED1, as well as structural genes, such as ACETYL-CoA CARBOXYLASE, ACYL-CoA DIACYLGLYCEROL ACYLTRANSFERASE, and LONG-CHAIN ACYL-CoA SYNTHETASES. We observed that several genes related to the phytohormones, gibberellins, jasmonate, and indole acetic acid, were differentially expressed in the NILs. Our findings provide a broad account of the numbers, distribution, and expression profiles of acyl lipid metabolism genes, as well as gene networks that potentially control oil accumulation in B. napus seeds. The upregulation of key regulatory and structural genes related to lipid biosynthesis likely plays a major role for the increased seed oil in YC13-559.

Subclinical endometritis (SCE) adversely affects fertility and is a diagnostic challenge in bovine practice. In the present study, it was hypothesized that SCE in cows influence the plasma levels of nitric oxide (NO), lipid peroxide (LPO) and polymorphonuclear (PMN) cell functions. Cows with SCE (n,12) were selected on the basis of positive colour reaction of cervico-vaginal mucus (CVM) to Whiteside test, alkaline pH of CVM and presence of > 5% PMN cells in uterine cytology smears. Cows without endometritis served as negative control (n,12). Functions of PMN cells were assessed by estimating superoxide (O2¯) and hydrogen peroxide (H2O2) production ability. Further, to assess the inflammatory status and oxidative stress, plasma levels of NO and LPO were measured. The results revealed that cows with SCE had significantly higher H2O2 (19.70±6.43 vs 2.52±0.71 nmol/2 × 106 cells/30 min incubation) in isolated blood PMN cells as compared to non endometritic cows (P

Currently, the treatment for ovarian cancer entails cytoreductive surgery followed by chemotherapy, mainly, carboplatin combined with paclitaxel. Although this regimen is initially effective in a high percentage of cases, unfortunately within few months of initial treatment, tumor relapse occurs because of platinum-resistance. This is attributed to chemo-resistance of cancer stem cells (CSCs). Herein we show for the first time that withaferin A (WFA), a bioactive compound isolated from the plant Withania somnifera, when used alone or in combination with cisplatin (CIS) targets putative CSCs. Treatment of nude mice bearing orthotopic ovarian tumors generated by injecting human ovarian epithelial cancer cell line (A2780) with WFA and cisplatin (WFA) alone or in combination resulted in a 70 to 80% reduction in tumor growth and complete inhibition of metastasis to other organs compared to untreated controls. Histochemical and Western blot analysis of the tumors revealed that inclusion of WFA (2 mg/kg) resulted in a highly significant elimination of cells expressing CSC markers - CD44, CD24, CD34, CD117 and Oct4 and downregulation of Notch1, Hes1 and Hey1 genes. In contrast treatment of mice with CIS alone (6 mg/kg) had opposite effect on those cells. Increase in cells expressing CSC markers and Notch1 signaling pathway in tumors exposed to CIS may explain recurrence of cancer in patients treated with carboplatin and paclitaxel. Since, WFA alone or in combination with CIS eliminates putative CSCs, we conclude that WFA in combination with CIS may present more efficacious therapy for ovarian cancer.

In this study, a new species of Alanomyces was isolated as an endophyte from the bark of Azadirachta indica from Mulshi, Maharashtra. The identity of this isolate was confirmed based on the asexual morphological characteristics as well as multi-gene phylogeny based on the internal transcribed spacer (ITS) and large subunit (LSU) nuclear ribosomal RNA (rRNA) regions. As this was the second species to be reported in this genus, we sequenced the genome of this species to increase our knowledge about the possible applicability of this genus to various industries. Its genome length was found to be 35.01 Mb, harboring 7870 protein-coding genes as per Augustus and 8101 genes using GeMoMa. Many genes were annotated using the Clusters of Orthologous Groups (COGs) database, the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), Swiss-Prot, NCBI non-redundant nucleotide sequences (NTs), and NCBI non-redundant protein sequences (NRs). The number of repeating sequences was predicted using Proteinmask and RepeatMasker; tRNA were detected using tRNAscan and snRNA were predicted using rfam_scan. The genome was also annotated using the Pathogen–Host Interactions Database (PHI-base) and AntiSMASH. To confirm the evolutionary history, average nucleotide identity (ANIb), phylogeny based on orthologous proteins, and single nucleotide polymorphisms (SNPs) were carried out. Metabolic profiling of the methanolic extract of dried biomass and ethyl acetate extract of the filtrate revealed a variety of compounds of great importance in the pharmaceutical and cosmetic industry. The characterization and genomic analysis of the newly discovered species Alanomyces manoharacharyi highlights its potential applicability across multiple industries, particularly in pharmaceuticals and cosmetics due to its diverse secondary metabolites and unique genetic features it possesses.

REST is abundantly expressed in mouse embryonic stem cells (ESCs). Many genome-wide analyses have found REST to be an integral part of the ESC pluripotency network. However, experimental systems have produced contradictory findings: (1) REST is required for the maintenance of ESC pluripotency and loss of REST causes increased expression of differentiation markers, (2) REST is not required for the maintenance of ESC pluripotency and loss of REST does not change expression of differentiation markers, and (3) REST is not required for the maintenance of ESC pluripotency but loss of REST causes decreased expression of differentiation markers. These reports highlight gaps in our knowledge of the ESC network.Employing biochemical and genome-wide analyses of various culture conditions and ESC lines, we have attempted to resolve some of the discrepancies in the literature.We show that Rest+/- and Rest-/- AB-1 mutant ESCs, which did not exhibit a role of REST in ESC pluripotency when cultured in the presence of feeder cells, did show impaired self-renewal when compared with the parental cells under feeder-free culture conditions, but only in early passage cells. In late passage cells, both Rest+/- and Rest-/- AB-1 ESCs restored pluripotency, suggesting a passage and culture condition-dependent response. Genome-wide analysis followed by biochemical validation supported this response and further indicated that the restoration of pluripotency was associated by increased expression of the ESC pluripotency factors. E14Tg2a.4 ESCs with REST-knockdown, which earlier showed a REST-dependent pluripotency when cultured under feeder-free conditions, as well as Rest-/- AB-1 ESCs, showed no REST-dependent pluripotency when cultured in the presence of either feeder cells or laminin, indicating that extracellular matrix components can rescue REST's role in ESC pluripotency.REST regulates ESC pluripotency in culture condition- and ESC line-dependent fashion and ESC pluripotency needs to be evaluated in a context dependent manner.

BackgroundDespite recent discoveries of new molecular targets and pathways, the search for an effective therapy for Glioblastoma Multiforme (GBM) continues. A newly emerged field, radiogenomics, links gene expression profiles with MRI phenotypes. MRI-FLAIR is a noninvasive diagnostic modality and was previously found to correlate with cellular invasion in GBM. Thus, our radiogenomic screen has the potential to reveal novel molecular determinants of invasion. Here, we present the first comprehensive radiogenomic analysis using quantitative MRI volumetrics and large-scale gene- and microRNA expression profiling in GBM.MethodsBased on The Cancer Genome Atlas (TCGA), discovery and validation sets with gene, microRNA, and quantitative MR-imaging data were created. Top concordant genes and microRNAs correlated with high FLAIR volumes from both sets were further characterized by Kaplan Meier survival statistics, microRNA-gene correlation analyses, and GBM molecular subtype-specific distribution.ResultsThe top upregulated gene in both the discovery (4 fold) and validation (11 fold) sets was PERIOSTIN (POSTN). The top downregulated microRNA in both sets was miR-219, which is predicted to bind to POSTN. Kaplan Meier analysis demonstrated that above median expression of POSTN resulted in significantly decreased survival and shorter time to disease progression (PConclusionHere, we propose a novel diagnostic method to screen for molecular cancer subtypes and genomic correlates of cellular invasion. Our findings also have potential therapeutic significance since successful molecular inhibition of invasion will improve therapy and patient survival in GBM.

New insecticides are urgently needed because resistance to current insecticides allows resurgence of disease-transmitting mosquitoes while concerns for human toxicity from current compounds are growing. We previously reported the finding of a free cysteine (Cys) residue at the entrance of the active site of acetylcholinesterase (AChE) in some insects but not in mammals, birds, and fish. These insects have two AChE genes (AP and AO), and only AP-AChE carries the Cys residue. Most of these insects are disease vectors such as the African malaria mosquito (Anopheles gambiae sensu stricto) or crop pests such as aphids. Recently we reported a Cys-targeting small molecule that irreversibly inhibited all AChE activity extracted from aphids while an identical exposure caused no effect on the human AChE. Full inhibition of AChE in aphids indicates that AP-AChE contributes most of the enzymatic activity and suggests that the Cys residue might serve as a target for developing better aphicides. It is therefore worth investigating whether the Cys-targeting strategy is applicable to mosquitocides. Herein, we report that, under conditions that spare the human AChE, a methanethiosulfonate-containing molecule at 6 microM irreversibly inhibited 95% of the AChE activity extracted from An. gambiae s. str. and >80% of the activity from the yellow fever mosquito (Aedes aegypti L.) or the northern house mosquito (Culex pipiens L.) that is a vector of St. Louis encephalitis. This type of inhibition is fast ( approximately 30 min) and due to conjugation of the inhibitor to the active-site Cys of mosquito AP-AChE, according to our observed reactivation of the methanethiosulfonate-inhibited AChE by 2-mercaptoethanol. We also note that our sulfhydryl agents partially and irreversibly inhibited the human AChE after prolonged exposure (>4 hr). This slow inhibition is due to partial enzyme denaturation by the inhibitor and/or micelles of the inhibitor, according to our studies using atomic force microscopy, circular dichroism spectroscopy, X-ray crystallography, time-resolved fluorescence spectroscopy, and liquid chromatography triple quadrupole mass spectrometry. These results support our view that the mosquito-specific Cys is a viable target for developing new mosquitocides to control disease vectors and to alleviate resistance problems with reduced toxicity toward non-target species.

Aphids, among the most destructive insects to world agriculture, are mainly controlled by organophosphate insecticides that disable the catalytic serine residue of acetylcholinesterase (AChE). Because these agents also affect vertebrate AChEs, they are toxic to non-target species including humans and birds. We previously reported that a cysteine residue (Cys), found at the AChE active site in aphids and other insects but not mammals, might serve as a target for insect-selective pesticides. However, aphids have two different AChEs (termed AP and AO), and only AP-AChE carries the unique Cys. The absence of the active-site Cys in AO-AChE might raise concerns about the utility of targeting that residue. Herein we report the development of a methanethiosulfonate-containing small molecule that, at 6.0 microM, irreversibly inhibits 99% of all AChE activity extracted from the greenbug aphid (Schizaphis graminum) without any measurable inhibition of the human AChE. Reactivation studies using beta-mercaptoethanol confirm that the irreversible inhibition resulted from the conjugation of the inhibitor to the unique Cys. These results suggest that AO-AChE does not contribute significantly to the overall AChE activity in aphids, thus offering new insight into the relative functional importance of the two insect AChEs. More importantly, by demonstrating that the Cys-targeting inhibitor can abolish AChE activity in aphids, we can conclude that the unique Cys may be a viable target for species-selective agents to control aphids without causing human toxicity and resistance problems.

Background Mutations in the LMNA gene, encoding LMNA (lamin A/C), causes distinct disorders, including dilated cardiomyopathies, collectively referred to as laminopathies. The genes (coding and noncoding) and regulatory pathways controlled by LMNA in the heart are not completely defined. Methods and Results We analyzed cardiac transcriptome from wild‐type, loss‐of‐function (Lmna−/−), and gain‐of‐function (Lmna−/− injected with adeno‐associated virus serotype 9 expressing LMNA) mice with normal cardiac function. Deletion of Lmna (Lmna−/−) led to differential expression of 2193 coding and 629 long noncoding RNA genes in the heart (q