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Olfactory receptors (ORs) which are mainly known as odor-sensors in the olfactory epithelium are shown to be expressed in several non-sensory tissues. Despite the specified role of some of these receptors in normal physiology of the kidney, little is known about their potential effect in renal disorders. In this study, using the holistic view of systems biology, it was determined that ORs are significantly changed during the progression of kidney fibrosis. For further validation, common differentially expressed ORs resulted from reanalysis of two time-course microarray datasets were selected for experimental evaluation in a validated murine model of unilateral ureteral obstruction (UUO). Transcriptional analysis by real-time quantitative polymerase chain reaction demonstrated considerable changes in the expression pattern of Olfr433, Olfr129, Olfr1393, Olfr161, and Olfr622 during the progression of kidney fibrosis. For localization of these ORs, single-cell RNA-sequencing datasets of normal and UUO mice were reanalyzed. Results showed that Olfr433 is highly expressed in macrophages in day-2 and 7 post-injury in UUO mice and not in normal subgroups. Besides, like previous findings, Olfr1393 was shown to be expressed prominently in the proximal tubular cells of the kidney. In conclusion, our combinatorial temporal approach to the underlying mechanisms of chronic kidney disease highlighted the potential role of ORs in progression of fibrosis. The expression of Olfr433 in the macrophages provides some clue about its relation to molecular mechanisms promoted in the fibrotic kidney. The proposed ORs in this study could be the subject of further functional assessments in the future.

Working memory (WM) is one of the most affected cognitive domains in multiple sclerosis (MS), which is mainly studied by the previously established binary model for information storage (slot model). Recent observations based on the continuous reproduction paradigms showed that assuming dynamic allocation of WM resources (resource model) instead of the binary hypothesis will give more accurate predictions in WM assessment. However, they have not been employed in the field of MS despite their influence in uncovering novel mechanistic insights into the WM organization. Here, by utilizing two continuous reproduction paradigms, we investigated WM dysfunction in MS. Also, by applying a computational model, the underlying structure of WM dysfunction was further explored. A total of 121 patients with MS (61 relapsing-remitting and 60 secondary progressive) and 73 healthy controls were enrolled in this study. The precision of visual WM was measured using memory-guided localization (MGL) and n-back paradigms. The classifying performance of these paradigms in distinguishing different groups was assessed using receiver operating characteristic analysis. Moreover, the sources of error in information recall were evaluated by computational modeling on n-back results. Our findings determined an overall decrease in recall precision and increased recall variability in MS. While the classifying performance of MGL was better in distinguishing MS subtypes, n-back paradigms were more accurate in discriminating healthy control from relapsing-remitting MS. The applied model showed that decreased signal-to-noise ratio and misbinding error were responsible for WM deficits in these patients. In conclusion, our results determined the magnitude of WM deficit and demonstrated misbinding error as an important component of WM dysfunction in MS. The dissociable functions of these paradigms in classifying MS subtypes provided evidence about the underlying mechanisms of WM deficits in progressive states of the disease.