Analysis of CRISPR‐Cas9 screens identifies genetic dependencies in melanoma

Targeting the MAPK signaling pathway has transformed the treatment of metastatic melanoma. CRISPR‐Cas9 genetic screens provide a genome‐wide approach to uncover novel genetic dependencies that might serve as therapeutic targets. Here, we analyzed recently reported CRISPR‐Cas9 screens comparing data from 28 melanoma cell lines and 313 cell lines of other tumor types in order to identify fitness genes related to melanoma. We found an average of 1,494 fitness genes in each melanoma cell line. We identified 33 genes, inactivation of which specifically reduced the fitness of melanoma. This set of tumor type‐specific genes includes established melanoma fitness genes as well as many genes that have not previously been associated with melanoma growth. Several genes encode proteins that can be targeted using available inhibitors. We verified that genetic inactivation of DUSP4 and PPP2R2A reduces the proliferation of melanoma cells. DUSP4 encodes an inhibitor of ERK, suggesting that further activation of MAPK signaling activity through its loss is selectively deleterious to melanoma cells. Collectively, these data present a resource of genetic dependencies in melanoma that may be explored as potential therapeutic targets.     

Sequential CRISPR gene editing in human iPSCs charts the clonal evolution of myeloid leukemia and identifies early disease targets

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Functional studies of CpSRP54 in diatoms show that the mechanism of thylakoid protein insertion differs from that in plants and green algae

The chloroplast signal recognition particle 54 kDa (CpSRP54) protein is a member of the CpSRP pathway known to target proteins to thylakoid membranes in plants and green algae. Loss of CpSRP54 in the marine diatom Phaeodactylum tricornutum lowers the accumulation of a selection of chloroplast-encoded subunits of photosynthetic complexes, indicating a role in the co-translational part of the CpSRP pathway. In contrast to plants and green algae, absence of CpSRP54 does not have a negative effect on the content of light-harvesting antenna complex proteins and pigments in P. tricornutum, indicating that the diatom CpSRP54 protein has not evolved to function in the post-translational part of the CpSRP pathway. Cpsrp54 KO mutants display altered photophysiological responses, with a stronger induction of photoprotective mechanisms and lower growth rates compared to wild type when exposed to increased light intensities. Nonetheless, their phenotype is relatively mild, thanks to the activation of mechanisms alleviating the loss of CpSRP54, involving upregulation of chaperones. We conclude that plants, green algae, and diatoms have evolved differences in the pathways for co-translational and post-translational insertion of proteins into the thylakoid membranes.     

Reducing psychological distress and depression in humanitarian emergencies: An essential role for nonspecialists

John Naslund and Eirini Karyotaki discuss Mark Jordans and colleagues’ accompanying research study on therapy for people with psychological distress in Nepal.

Humanitarian emergencies such as war, natural disasters, or pandemics profoundly disrupt the daily lives of those impacted and result in psychological distress and high risk of mental disorders. With increasing frequency of humanitarian emergencies over the past decade, including the most recent Coronavirus Disease 2019 (COVID-19) pandemic, there is immediate need for brief scalable interventions that can be readily delivered to at-risk population groups [1]. With the dearth of available mental health specialists, especially in low-resource settings susceptible to crises, natural disasters, or displacement, combined with fragmented or poor functioning health systems during emergencies, nonspecialists may be ideally positioned to deliver such programs [2]. Nonspecialists, such as community health workers or lay persons, do not have specialty training in mental healthcare; yet, these frontline providers often play an essential role in delivering primary care services in many low- and middle-income countries [3,4], and they are increasingly being recognized as critical for scaling up access to psychological treatments for mental disorders [5,6]. Further, in a humanitarian crisis, use of nonspecialists from the affected population offers key benefits, such as empowering community members and drawing upon the experience of facilitators [7].In an accompanying study in PLOS Medicine, Mark Jordans and colleagues demonstrate that community members with no prior mental health training could effectively deliver the WHO Group Problem Management Plus (Group PM+) program in a humanitarian setting in Nepal [8]. The research team conducted a cluster randomized controlled trial enrolling 72 wards and found that the 5-session Group PM+ delivered by nonspecialists contributed to reduction in psychological distress and depressive symptoms when compared to usual care. There may be opportunities to expand on these findings and further advance task sharing efforts in humanitarian settings.     

Viral Detection: Past,Present, and Future

Viruses are essentially composed of a nucleic acid (segmented or not, DNA, or RNA) and a protein coat. Despite their simplicity, these small pathogens are responsible for significant economic and humanitarian losses that have had dramatic consequences in the course of human history. Since their discovery, scientists have developed different strategies to efficiently detect viruses, using all possible viral features. Viruses shape, proteins, and nucleic acid are used in viral detection. In this review, the development of these techniques, especially for plant and mammalian viruses, their strengths and weaknesses as well as the latest cutting‐edge technologies that may be playing important roles in the years to come are described.