RESUMEN
Small- and medium-scale farmer's typically follow polyculture or diverse crop cultivation. However, cultivation of diverse crops in small area can cause cross infection leading to disease spreading across crops. A microplot-based field study was conducted to understand the disease susceptibility and disease mobility across various crops, including tomato, chilli, mungbean, and bitter gourd. The mungbean yellow mosaic virus (MYMV) incidence was noted first in the mungbean crop followed by tomato leaf curl New Delhi virus (ToLCNDV) in tomato and chilli leaf curl virus (ChLCV) in chilli crop. Interestingly, bitter gourd crop was infected lastly with symptoms including yellow and green mottling, severe leaf curling, and stunted growth. However, in bitter gourd crop symptoms, like typical leaf curl virus, could not be conclusively related to a certain type of begomovirus. Molecular diagnosis using begomovirus specific deng primers and coat protein (CP) gene primers specific to begomovirus species revealed the presence of ToLCNDV in bitter gourd samples. The phylogenetic analysis of CP gene sequences revealed 98 per cent nucleotide identity with ToLCNDV. Further cross infectivity assays confirmed the transmission of ToLCNDV from tomato to bitter gourd and vice versa. The cryptic species of whiteflies isolated from the bitter gourd fields were sequence confirmed to belong to Asia-I genetic group that were reported to transmit ToLCNDV previously. Overall, our study suggests the vulnerability of bitter gourd crop for ToLCNDV infection when cultivated by the side of tomato plots. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-02975-6.
RESUMEN
While the role of mitochondrial metabolism in controlling T-lymphocyte activation and function is becoming more clear, the specifics of how mitochondrial redox signaling contributes to T-lymphocyte regulation remains elusive. Here, we examined the global effects of elevated mitochondrial superoxide (O2-) on T-lymphocyte activation using a novel model of inducible manganese superoxide dismutase (MnSOD) knock-out. Loss of MnSOD led to specific increases in mitochondrial O2- with no evident changes in hydrogen peroxide (H2O2), peroxynitrite (ONOO-), or copper/zinc superoxide dismutase (CuZnSOD) levels. Unexpectedly, both mitochondrial and glycolytic metabolism showed significant reductions in baseline, maximal capacities, and ATP production with increased mitochondrial O2- levels. MnSOD knock-out T-lymphocytes demonstrated aberrant activation including widespread dysregulation in cytokine production and increased cellular apoptosis. Interestingly, an elevated proliferative signature defined by significant upregulation of cell cycle regulatory genes was also evident in MnSOD knock-out T-lymphocytes, but these cells did not show accelerated proliferative rates. Global disruption in T-lymphocyte DNA methylation and hydroxymethylation was also observed with increased mitochondrial O2-, which was correlated to alterations in intracellular metabolite pools linked to the methionine cycle. Together, these results demonstrate a mitochondrial redox and metabolic couple that when disrupted may alter cellular processes necessary for proper T-lymphocyte activation.
Asunto(s)
Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/metabolismo , Epigénesis Genética/fisiología , Mitocondrias/metabolismo , Superóxidos/metabolismo , Animales , Citocinas/metabolismo , Metilación de ADN/fisiología , Peróxido de Hidrógeno/metabolismo , Activación de Linfocitos/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Oxidación-Reducción , Estrés Oxidativo/fisiología , Transducción de Señal/fisiología , Superóxido Dismutasa/metabolismoRESUMEN
Current treatment for recurrent and aggressive/anaplastic thyroid cancers is ineffective. Novel targeted therapies aimed at the inhibition of the mutated oncoprotein BRAF(V600E) have shown promise in vivo and in vitro but do not result in cellular apoptosis. TNF-related apoptosis-inducing ligand (TRAIL) induces apoptosis in a tumor-selective manner by activating the extrinsic apoptotic pathway. Here, we show that a TRAIL-R2 agonist antibody, lexatumumab, induces apoptosis effectively in some thyroid cancer cell lines (HTh-7, TPC-1 and BCPAP), while more aggressive anaplastic cell lines (8505c and SW1736) show resistance. Treatment of the most resistant cell line, 8505c, using lexatumumab in combination with the BRAF(V600E) inhibitor, PLX4720, and the PI3K inhibitor, LY294002, (triple-drug combination) sensitizes the cells by triggering both the extrinsic and intrinsic apoptotic pathways in vitro as well as 8505c orthotopic thyroid tumors in vivo. A decrease in anti-apoptotic proteins, pAkt, Bcl-xL, Mcl-1 and c-FLIP, coupled with an increase in the activator proteins, Bax and Bim, results in an increase in the Bax to Bcl-xL ratio that appears to be critical for sensitization and subsequent apoptosis of these resistant cells. Our results suggest that targeting the death receptor pathway in thyroid cancer can be a promising strategy for inducing apoptosis in thyroid cancer cells, although combination with other kinase inhibitors may be needed in some of the more aggressive tumors initially resistant to apoptosis.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Apoptosis/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Inhibidores de las Quinasa Fosfoinosítidos-3 , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Neoplasias de la Tiroides/tratamiento farmacológico , Animales , Anticuerpos Monoclonales/administración & dosificación , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Línea Celular Tumoral , Cromonas/administración & dosificación , Relación Dosis-Respuesta a Droga , Resistencia a Antineoplásicos/genética , Femenino , Perfilación de la Expresión Génica , Humanos , Indoles/administración & dosificación , Ratones , Ratones SCID , Terapia Molecular Dirigida , Morfolinas/administración & dosificación , Fosfatidilinositol 3-Quinasa/metabolismo , Inhibidores de Proteínas Quinasas/administración & dosificación , Proteínas Proto-Oncogénicas B-raf/antagonistas & inhibidores , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas B-raf/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Interferencia de ARN , Sulfonamidas/administración & dosificación , Neoplasias de la Tiroides/enzimología , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología , Factores de Tiempo , Transfección , Carga Tumoral/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Four instances are presented of self-amputation of the pinna of the external ear carried out by three right-handed, white males between January 1993 and May 1993. The common characteristics of these subjects--two men with personality disorder and one with schizophrenia--are discussed and compared with other examples of self-mutilation involving the face and ears, including that of van Gogh. A survey of Australian and New Zealand prisons was conducted to determine the frequency of this form of self-mutilation within the last five years, and yielded only one other case. Connections exist between the amputees supporting the notion that self-mutilation is "contagious"; the relevance of this to issues of management is considered.