<em>DAAM2</em> variants cause nephrotic syndrome via actin dysregulation.

The discovery of &gt;60 monogenic causes of nephrotic syndrome (NS) has revealed a central role for the actin regulators RhoA/Rac1/Cdc42 and their effectors, including the formin INF2. By whole-exome sequencing (WES), we here discovered bi-allelic variants in the formin DAAM2 in four unrelated families with steroid-resistant NS. We show that DAAM2 localizes to the cytoplasm in podocytes and in kidney sections. Further, the variants impair DAAM2-dependent actin remodeling processes: wild-type DAAM2 cDNA, but not cDNA representing missense variants found in individuals with NS, rescued reduced podocyte migration rate (PMR) and restored reduced filopodia formation in shRNA-induced DAAM2-knockdown podocytes. Filopodia restoration was also induced by the formin-activating molecule IMM-01. DAAM2 also co-localizes and co-immunoprecipitates with INF2, which is intriguing since variants in both formins cause NS. Using in&nbsp;vitro bulk and TIRF microscopy assays, we find that DAAM2 variants alter actin assembly activities of the formin. In a Xenopus daam2-CRISPR knockout model, we demonstrate actin dysregulation in&nbsp;vivo and glomerular maldevelopment that is rescued by WT-DAAM2 mRNA. We conclude that DAAM2 variants are a likely cause of monogenic human SRNS due to actin dysregulation in podocytes. Further, we provide evidence that DAAM2-associated SRNS may be amenable to treatment using actin regulating compounds

A food-manufacturing manager’s experiences and perceptions of the implementation of an incentive scheme

Orientation: The field researcher, under the supervision of the co-authors Bussin and Schurink, sought to explore the experiences, views and perceptions of 10 managers about the incentive scheme that a South African food manufacturing company introduced. Research purpose: Identifying the contributors to negative feelings and demotivation, or conversely, excitement and motivation, will ultimately assist managers to implement an incentive scheme to motivate staff and improve performance. Motivation for the study: There is little research on how participants perceive incentive schemes and whether or not they motivate employees and improve overall performance. Research design, approach and method: The researcher used a modernistic qualitative research approach and, more specifically, a case study. Main findings: The participants in the research were unaware of the performance goals they needed to achieve. They felt that there was no link between their performance and their earnings. They felt that some objectives were demeaning and insulting, as was the payment they received. They felt that achieving their goals was outside their control and influence. Practical/managerial implications: Participants felt excited and motivated to perform when their managers presented the department’s overall goals to them and asked the participants to set their own goals based on the department’s objectives. Contribution/value-add: Although this study is explorative and descriptive, it suggests that it is how departments implement an incentive scheme, rather than merely having one, that will motivate or demotivate employees to perform