Unpicking the Roles of DNA Damage Protein Kinases in Trypanosomatids

To preserve genome integrity when faced with DNA lesions, cells activate and coordinate a multitude of DNA repair pathways to ensure timely error correction or tolerance, collectively called the DNA damage response (DDR). These interconnecting damage response pathways are molecular signal relays, with protein kinases (PKs) at the pinnacle. Focused efforts in model eukaryotes have revealed intricate aspects of DNA repair PK function, including how they direct DDR pathways and how repair reactions connect to wider cellular processes, including DNA replication and transcription. The Kinetoplastidae, including many parasites like Trypanosoma spp. and Leishmania spp. (causative agents of debilitating, neglected tropical infections), exhibit peculiarities in several core biological processes, including the predominance of multigenic transcription and the streamlining or repurposing of DNA repair pathways, such as the loss of non-homologous end joining and novel operation of nucleotide excision repair (NER). Very recent studies have implicated ATR and ATM kinases in the DDR of kinetoplastid parasites, whereas DNA-dependent protein kinase (DNA-PKcs) displays uncertain conservation, questioning what functions it fulfills. The wide range of genetic manipulation approaches in these organisms presents an opportunity to investigate DNA repair kinase roles in kinetoplastids and to ask if further kinases are involved. Furthermore, the availability of kinase inhibitory compounds, targeting numerous eukaryotic PKs, could allow us to test the suitability of DNA repair PKs as novel chemotherapeutic targets. Here, we will review recent advances in the study of trypanosomatid DNA repair kinases.

Large-scale identification of ubiquitination sites on membrane-associated proteins in Arabidopsis thaliana seedlings

Protein phosphorylation and ubiquitination are two of the most abundant forms of post-translational modifications in eukaryotes, regulated by thousands of protein kinases, phosphatases, E3 ubiquitin ligases, and ubiquitin proteases. Although previous studies have catalogued several ubiquitinated proteins in plants (Walton et al., 2016), few membrane-localized proteins have been identified. Receptor kinases (RKs) initiate phosphorylation signal relays that regulate plant growth, development, and stress responses. While the regulatory role of phosphorylation on protein kinase function is well-documented (Couto and Zipfel, 2016), considerably less is known about the role of ubiquitination on protein kinase function, even though protein turnover is critical to their signaling competence and cellular homeostasis. Here we describe the large-scale identification of ubiquitination sites on Arabidopsis proteins associated with or integral to the plasma membrane, including over 100 protein kinases.

Distributing UAVs as Wireless Repeaters in Disaster Relief via Group Role Assignment

When an earthquake occurs, disaster relief is an urgent, complex and critical mission. High on the list is communication network recovery within the disaster area. Unmanned aerial vehicles (UAVs) are often used in this regard. Some of them are used as collective repeaters to provide the required network coverage. Their timely, efficient, and collaborative deployment to specific locations is a big challenge. To meet this challenge, this paper formalizes and solves the problem of UAV deployment for signal relays via group role assignment (GRA). The minimum spanning tree algorithm is used to model a rapidly deployed optimal relay network. It can help establish the minimum number of relay points necessary to ensure communication stability. In this scenario, UAVs (agents) adopt roles as communication relays. The task of distributing UAVs to relay points can be solved quickly via the assignment process of GRA, which can solve the x-ILP problem with the help of the PuLP package of Python. Results from thousands of experimental simulations indicate that our solutions are effective, robust and practical. The process can be used to establish an optimal, efficient, and collaborative relay network using UAVs. Their rapid deployment can be a significant contribution to earthquake disaster relief.

Music for Cochlear Implants

This paper examines compositions and performances created by scientists and musicians who seek to make music for cochlear implants, surgically implanted assistive medical technologies used by many hard-of-hearing and deaf people. The implant employs a microphone to capture an audio signal, which is then divided into frequency bands and transmitted to a receiver emplaced in a recipient’s skull, behind the ear. The implant provides poor reproduction of those timbral features of sound central to many normative experiences and expectations of music. Compositions and performances for implant users seek either (1) to improve the way the implant processes frequency, (2) to create music that works well with an implant’s available frequency profile, or (3) to access the implant directly, crafting music specially tailored for the implant through the device’s signal relays. Critically assaying such projects, this paper reevaluates and recontextualizes what can count as timbre in diverse deaf and hearing worlds.