Harnessing the role of mitogen-activated protein kinases against abiotic stresses in plants

Crop plants are vulnerable to various biotic and abiotic stresses, whereas plants tend to retain their physiological mechanisms by evolving cellular regulation. To mitigate the adverse effects of abiotic stresses, many defense mechanisms are induced in plants. One of these mechanisms is the mitogen-activated protein kinase (MAPK) cascade, a signaling pathway used in the transduction of extracellular stimuli into intercellular responses. This stress signaling pathway is activated by a series of responses involving MAPKKKs→MAPKKs→MAPKs, consisting of interacting proteins, and their functions depend on the collaboration and activation of one another by phosphorylation. These proteins are key regulators of MAPK in various crop plants under abiotic stress conditions and also related to hormonal responses. It is revealed that in response to stress signaling, MAPKs are characterized as multigenic families and elaborate the specific stimuli transformation as well as the antioxidant regulation system. This pathway is directed by the framework of proteins and stopping domains confer the related associates with unique structure and functions. Early studies of plant MAPKs focused on their functions in model plants. Based on the results of whole-genome sequencing, many MAPKs have been identified in plants, such as Arbodiposis, tomato, potato, alfalfa, poplar, rice, wheat, maize, and apple. In this review, we summarized the recent work on MAPK response to abiotic stress and the classification of MAPK cascade in crop plants. Moreover, we highlighted the modern research methodologies such as transcriptomics, proteomics, CRISPR/Cas technology, and epigenetic studies, which proposed, identified, and characterized the novel genes associated with MAPKs and their role in plants under abiotic stress conditions. In-silico-based identification of novel MAPK genes also facilitates future research on MAPK cascade identification and function in crop plants under various stress conditions

Nuclear Receptor Rev-erb Alpha (Nr1d1) Functions in Concert with Nr2e3 to Regulate Transcriptional Networks in the Retina

The majority of diseases in the retina are caused by genetic mutations affecting the development and function of photoreceptor cells. The transcriptional networks directing these processes are regulated by genes such as nuclear hormone receptors. The nuclear hormone receptor gene Rev-erb alpha/Nr1d1 has been widely studied for its role in the circadian cycle and cell metabolism, however its role in the retina is unknown. In order to understand the role of Rev-erb alpha/Nr1d1 in the retina, we evaluated the effects of loss of Nr1d1 to the developing retina and its co-regulation with the photoreceptor-specific nuclear receptor gene Nr2e3 in the developing and mature retina. Knock-down of Nr1d1 expression in the developing retina results in pan-retinal spotting and reduced retinal function by electroretinogram. Our studies show that NR1D1 protein is co-expressed with NR2E3 in the outer neuroblastic layer of the developing mouse retina. In the adult retina, NR1D1 is expressed in the ganglion cell layer and is co-expressed with NR2E3 in the outer nuclear layer, within rods and cones. Several genes co-targeted by NR2E3 and NR1D1 were identified that include: Nr2c1, Recoverin, Rgr, Rarres2, Pde8a, and Nupr1. We examined the cyclic expression of Nr1d1 and Nr2e3 over a twenty-four hour period and observed that both nuclear receptors cycle in a similar manner. Taken together, these studies reveal a novel role for Nr1d1, in conjunction with its cofactor Nr2e3, in regulating transcriptional networks critical for photoreceptor development and function

Socioeconomic determinants of psychotropic drug utilisation among elderly: a national population-based cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Psychotropic drugs are commonly utilised among the elderly. This study aimed to analyse whether two socioeconomic determinants - income and marital status - are associated with differences in utilisation of psychotropic drugs and potentially inappropriate psychotropic drugs among elderly in Sweden.</p> <p>Methods</p> <p>All individuals aged 75 years and older who had purchased a psychotropic drug in Sweden during 2006 were included (68.7% women, n = 384712). Data was collected from national individual-based registers. Outcome measures were utilisation of three or more psychotropic drugs and utilisation of potentially inappropriate psychotropic drugs, as classified by the Swedish National Board of Health and Welfare.</p> <p>Results</p> <p>Individuals with low income were more likely to utilise three or more psychotropic drugs compared to those with high income; adjusted odds ratio (aOR) 1.12 (95% confidence interval [CI] 1.10-1.14). The non-married had a higher probability for utilising three or more psychotropic drugs compared to the married (aOR 1.22; CI 1.20-1.25). The highest probability was observed among the divorced and the never married. Potentially inappropriate psychotropic drugs were more common among individuals with low compared to high income (aOR 1.14; CI 1.13-1.16). Compared to the married, potentially inappropriate psychotropic drug utilisation occurred more commonly among the non-married (aOR 1.08; CI 1.06-1.10). The never married and the divorced had the highest probability.</p> <p>Conclusions</p> <p>There was an association between socioeconomic determinants and psychotropic drug utilisation. The probability for utilising potentially inappropriate psychotropics was higher among individuals with low income and among the non-married.</p

Gain control network conditions in early sensory coding

Gain control is essential for the proper function of any sensory system. However, the precise mechanisms for achieving effective gain control in the brain are unknown. Based on our understanding of the existence and strength of connections in the insect olfactory system, we analyze the conditions that lead to controlled gain in a randomly connected network of excitatory and inhibitory neurons. We consider two scenarios for the variation of input into the system. In the first case, the intensity of the sensory input controls the input currents to a fixed proportion of neurons of the excitatory and inhibitory populations. In the second case, increasing intensity of the sensory stimulus will both, recruit an increasing number of neurons that receive input and change the input current that they receive. Using a mean field approximation for the network activity we derive relationships between the parameters of the network that ensure that the overall level of activity of the excitatory population remains unchanged for increasing intensity of the external stimulation. We find that, first, the main parameters that regulate network gain are the probabilities of connections from the inhibitory population to the excitatory population and of the connections within the inhibitory population. Second, we show that strict gain control is not achievable in a random network in the second case, when the input recruits an increasing number of neurons. Finally, we confirm that the gain control conditions derived from the mean field approximation are valid in simulations of firing rate models and Hodgkin-Huxley conductance based models

Zoonotic Tuberculosis – The Changing Landscape

Despite slow reductions in the annual burden of active human tuberculosis (TB) cases, zoonotic TB (zTB) remains a poorly monitored and an important unaddressed global problem. There is a higher incidence in some regions and countries, especially where close association exists between growing numbers of cattle (the major source of Mycobacterium bovis) and people, many suffering from poverty, and where dairy products are consumed unpasteurised. More attention needs to be focused on possible increased zTB incidence resulting from growth in dairy production globally and increased demand in low income countries in particular. Evidence of new zoonotic mycobacterial strains in South Asia and Africa (e.g. M. orygis), warrants urgent assessment of prevalence, potential drivers and risk in order to develop appropriate interventions. Control of M. bovis infection in cattle through detect and cull policies remain the mainstay of reducing zTB risk, whilst in certain circumstances animal vaccination is proving beneficial. New point of care diagnostics will help to detect animal infections and human cases. Given the high burden of human tuberculosis (caused by M. tuberculosis) in endemic areas, animals are affected by reverse zoonosis, including multi-drug resistant strains. This, may create drug resistant reservoirs of infection in animals. Like COVID-19, zTB is evolving in an ever-changing global landscape

Dopaminergic and Serotonergic Drug Use: A Nationwide Register-Based Study of Over 1 300 000 Older People

Objective: To investigate the use of dopaminergic and serotonergic drugs in elderly people. Methods: We analyzed data on age, sex and dispensed drugs for individuals aged $65 years registered in the Swedish Prescribed Drug Register from July to September 2008 (n = 1 347 564; 81$65 years in Sweden). Main outcome measures were dopaminergic (enhancing and/or lowering) and serotonergic (enhancing and/or lowering) drugs and combinations of these. Results: Dopaminergic and serotonergic drugs were used by 5.6 % and 13.2 % the participants, respectively. Female gender was related to use of both dopaminergic and, particularly, serotonergic drugs. Higher age was associated with use of dopamine lowering drugs and serotonergic drugs, whereas the association with use of dopamine enhancing drugs declined in the oldest old. The occurrence of combinations of dopaminergic and serotonergic drugs was generally low, with dopamine lowering + serotonin lowering drug the most common combination (1.6%). Female gender was associated with all of the combinations of dopaminergic and serotonergic drugs, whereas age showed a mixed pattern. Conclusion: Approximately one out of ten older patients uses serotonergic drugs and one out of twenty dopaminergic drugs. The frequent use of dopaminergic and serotonergic drugs in the elderly patients is a potential problem due to the fact that aging is associated with a down-regulation of both these monoaminergic systems. Future studies are needed fo