Pain and depression comorbidity causes asymmetric plasticity in the locus coeruleus neurons

There is strong comorbidity between chronic pain and depression, although the neural circuits and mechanisms underlying this association remain unclear. By combining immunohistochemistry, tracing studies and western blotting, with the use of different DREADDS (designer receptor exclusively activated by designer drugs) and behavioural approaches in a rat model of neuropathic pain (chronic constriction injury), we explore how this comorbidity arises. To this end, we evaluated the time-dependent plasticity of noradrenergic locus coeruleus neurons relative to the site of injury: ipsilateral (LCipsi) or contralateral (LCcontra) locus coeruleus at three different time points: short (2 days), mid (7 days) and long term (30-35 days from nerve injury). Nerve injury led to sensorial hypersensitivity from the onset of injury, whereas depressive-like behaviour was only evident following long-term pain. Global chemogenetic blockade of the LCipsi system alone increased short-term pain sensitivity while the blockade of the LCipsi or LCcontra relieved pain-induced depression. The asymmetric contribution of locus coeruleus modules was also evident as neuropathy develops. Hence, chemogenetic blockade of the LCipsi -> spinal cord projection, increased pain-related behaviours in the short term. However, this lateralized circuit is not universal as the bilateral chemogenetic inactivation of the locus coeruleus-rostral anterior cingulate cortex pathway or the intra-rostral anterior cingulate cortex antagonism of alpha1- and alpha2-adrenoreceptors reversed long-term pain-induced depression. Furthermore, chemogenetic locus coeruleus to spinal cord activation, mainly through LCipsi, reduced sensorial hypersensitivity irrespective of the time post-injury. Our results indicate that asymmetric activation of specific locus coeruleus modules promotes early restorative analgesia, as well as late depressive-like behaviour in chronic pain and depression comorbidity.This study was supported by grants cofinanced by the 'Fondo Europeo de Desarrollo Regional' (FEDER)-UE 'A way to build Europe' from the `Ministerio de Economia y Competitividad' (MINECO: RTI2018-099778-B-I00) and by the 'Ministerio de SaludInstituto de Salud Carlos III' (PI18/01691); the 'Consejeria de Salud de la Junta de Andalucia' (PI-0134-2018); the 'Programa Operativo de Andalucia FEDER, Iniciativa Territorial Integrada ITI 2014-2020 Consejeria Salud, Junta de Andalucia' (PI-0080-2017); the "Consejeri ' a de Transformacion Economica, Industria, Conocimiento y Universidades, Junta de Andalucia" (PEMP-00082020), Instituto de Investigacion e Innovacion en Ciencias Biomedicas de Cadiz (INiBICA LI19/06IN-CO22); the `Consejeri ' a de Economia, Innovacion, Ciencia y Empleo de la Junta de Andalucia' (CTS-510); the 'Centro de Investigacion Biomedica en Red de Salud Mental-CIBERSAM' (CB/07/09/0033) and the Academy of Finland (315043)

Faisán S2016: nueva variedad de trigo harinero de gluten débil para El Bajío

FaisanS2016 is a variety of soft wheat whose flour is useful for the biscuit industry or for use in mixtures to improve strong gluten wheats. It is moderately resistant to yellow rust and shows great stability over a wide range of planting dates and irrigation schedules. Its yield exceeded by 16.8 and 18.6% the varieties of soft wheats Urbina S2007 and Maya S2007, released in 2007 and up to 21% Cortazar S94, the most sown variety in El Bajío. obtained the title of breeder, being protected until May 18, 2032; it is also registered and published in the national catalog of plant varieties, which makes it possible to consider it in the seed qualification and production programs.Faisán S2016 es una variedad de trigo suave cuya harina es útil para la industria galletera o para utilizarla en mezclas para mejorar trigos de gluten fuerte. Es moderadamente resistente a la roya amarilla y muestra gran estabilidad en un amplio rango de fechas de siembra y calendarios de riego. Su rendimiento superó en 16.8 y 18.6% a las variedades de trigos suaves Urbina S2007 y Maya S2007, liberadas en 2007 y hasta con 21% a Cortazar S94, la variedad más sembrada en El Bajío. obtuvo el título de obtentor, quedando protegida hasta el 18 de mayo de 2032; asimismo, está registrada y publicada en el catálogo nacional de variedades vegetales, con lo cual es posible considerarla en los programas de calificación y producción de semillas

NME1 and DCC variants are associated with susceptibility and tumor characteristics in Mexican patients with colorectal cancer

Abstract Background Colorectal cancer (CRC) ranks third in cancer incidence globally and is the second leading cause of cancer-related mortality. The nucleoside diphosphate kinase 1 (NME1) and netrin 1 receptor (DCC) genes have been associated with resistance against tumorigenesis and tumor metastasis. This study investigates the potential association between NME1 (rs34214448 G > T and rs2302254 C > T) and DCC (rs2229080 G > C and rs714 A > G) variants and susceptibility to colorectal cancer development. Methods Samples from 232 colorectal cancer patients and 232 healthy blood donors underwent analysis. Variants were identified using polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) methodology. Associations were assessed using odds ratios (OR), and the p values were adjusted with Bonferroni test. Results Individuals carrying the G/T and T/T genotypes for the NME1 rs34214448 variant exhibited a higher susceptibility for develop colorectal cancer (OR = 2.68, 95% CI: 1.76–4.09, P = 0.001 and OR = 2.47, 95% CI: 1.37–4.47, P = 0.001, respectively). These genotypes showed significant associations in patients over 50 years (OR = 2.87, 95% CI: 1.81–4.54, P = 0.001 and OR = 2.99, 95% CI: 1.54–5.79, P = 0.001 respectively) and with early Tumor-Nodule-Metastasis (TNM) stage (P = 0.001), and tumor location in the rectum (P = 0.001). Furthermore, the DCC rs2229080 variant revealed that carriers of the G/C genotype had an increased risk for develop colorectal cancer (OR = 2.00, 95% CI: 1.28–3.11, P = 0.002) and were associated with age over 50 years, sex, and advanced TNM stages (P = 0.001). Conclusions These findings suggest that the NME1 rs34214448 and DCC rs2229080 variants play a significant role in colorectal cancer development