scholarly journals Evolutionary rate covariation identifies SLC30A9 (ZnT9) as a mitochondrial zinc transporter

2021 ◽  
Author(s):  
Amanda Kowalczyk ◽  
Omotola Gbadamosi ◽  
Kathryn Kolor ◽  
Jahree Sosa ◽  
Claudette St Croix ◽  
...  

AbstractRecent advances in genome sequencing have led to the identification of new ion and metabolite transporters, many of which have not been characterized. Due to the variety of subcellular localizations, cargo and transport mechanisms, such characterization is a daunting task, and predictive approaches focused on the functional context of transporters are very much needed. Here we present a case for identifying a transporter localization using evolutionary rate covariation (ERC), a computational approach based on pairwise correlations of amino acid sequence evolutionary rates across the mammalian phylogeny. As a case study, we find that poorly characterized transporter SLC30A9 (ZnT9) uniquely and prominently coevolves with several components of the mitochondrial oxidative phosphorylation chain, suggesting mitochondrial localization. We confirmed this computational finding experimentally using recombinant human SLC30A9. SLC30A9 loss caused zinc mishandling in the mitochondria, suggesting that under normal conditions it acts as a zinc exporter. We therefore propose that ERC can be used to predict the functional context of novel transporters and other poorly characterized proteins.

2021 ◽  
Author(s):  
Amanda Kowalczyk ◽  
Omotola Gbadamosi ◽  
Kathryn Kolor ◽  
Jahree Sosa ◽  
Livia Andrzejczuk ◽  
...  

Recent advances in genome sequencing have led to the identification of new ion and metabolite transporters, many of which have not been characterized. Due to the variety of subcellular localizations, cargo and transport mechanisms, such characterization is a daunting task, and predictive approaches focused on the functional context of transporters are very much needed. Here we present a case for identifying a transporter localization using evolutionary rate covariation (ERC), a computational approach based on pairwise correlations of amino acid sequence evolutionary rates across the mammalian phylogeny. As a case study, we find that poorly characterized transporter SLC30A9 (ZnT9) coevolves with several components of the mitochondrial oxidative phosphorylation chain, suggesting mitochondrial localization. We confirmed this computational finding experimentally using recombinant human SLC30A9. SLC30A9 loss caused zinc mishandling in the mitochondria, suggesting that under normal conditions it acts as a zinc exporter. We therefore propose that ERC can be used to predict the functional context of novel transporters and other poorly characterized proteins.


Author(s):  
Ian Rouse ◽  
David Power ◽  
Erik G. Brandt ◽  
Matthew Schneemilch ◽  
Konstantinos Kotsis ◽  
...  

We present a multiscale computational approach for the first-principles study of bio-nano interactions. Using titanium dioxide as a case study, we evaluate the affinity of titania nanoparticles to water and biomolecules through atomistic and coarse-grained techniques.


2019 ◽  
Vol 5 (1) ◽  
pp. 444-467
Author(s):  
Katherine A. Crawford

AbstractOstia, the ancient port of Rome, had a rich religious landscape. How processional rituals further contributed to this landscape, however, has seen little consideration. This is largely due to a lack of evidence that attests to the routes taken by processional rituals. The present study aims to address existing problems in studying processions by questioning what factors motivated processional movement routes. A novel computational approach that integrates GIS, urban network analysis, and agent-based modelling is introduced. This multi-layered approach is used to question how spectators served as attractors in the creation of a processional landscape using Ostia’s Campo della Magna Mater as a case study. The analysis of these results is subsequently used to gain new insight into how a greater processional landscape was created surrounding the sanctuary of the Magna Mater.


Author(s):  
Arvind Keprate ◽  
R. M. Chandima Ratnayake

Selecting a riser concept for FPSOs stationed in deep water has posed challenges, due to the high hydrostatic pressure and large vessel payload. One of the major factors governing the riser concept selection for deepwater FPSOs is the geographical location and weather conditions prevalent in the region. For example, the free hanging flexible riser has been mostly used in the moderate environments of offshore Brazil, while concepts like the SCR and Hybrid Riser Tower (HRT) are dominant in the calm weather conditions of the West of Africa (WoA). Selecting a riser concept for an FPSO stationed in harsh weather conditions like those of the Northern Norwegian Sea is a daunting task. This is due to the large vessel offsets and dynamics, which are directly transferred along the riser’s length to its base, thereby causing considerable fatigue damage to the riser. The main aim of this paper is to recommend a suitable riser concept, which may be hooked to an internal turret moored FPSO stationed in water of 1500m depth and in the harsh environmental conditions of the Northern Norwegian Sea. The recommendations are based on the literature review and the case study performed in the manuscript. On the basis of the literature review, a lazy wave configuration of flexible riser and Steel Lazy Wave Riser (SLWR) has been considered as a viable riser concept. Thereafter, a case study is performed to compare the two riser concepts, on the basis of vessel payload, fabrication cost and installation cost.


Author(s):  
Manu Venugopal

The drug development phase is one of the most time-consuming and expensive stages in the lifecycle of a drug. Marred by patent expirations, price regulations, complexities in disease conditions, life sciences companies are facing a daunting task to bring new molecular entities into the market. Digital health technologies are playing a critical role in addressing some of the challenges faced during drug development. In this chapter, the author talks about the challenges and key trends in the world of drug development, use of new digital health technologies, and the future of drug development. As an example, the author dives into a specific case study on the use of virtual assistants in clinical trials and the benefits of its usage on patients, healthcare professionals, and life sciences companies.


Author(s):  
Regina Gavin Williams

This case study examines the life of Rose, a 17-year-old junior attending a public high school in a southeastern city. In the state where Rose resides, the year of “aging-out” of the foster care system is 18-years-old. With the age of 18 being such a pivotal year, Rose must not only think about her potential post-secondary options, but her ability to achieve adult self-sufficiency at such a young age as well. With no supports, this proves to be a daunting task for Rose. It becomes Rose's thorn. This chapter will explore the career and college readiness self-efficacy of Rose as she navigates her post-secondary options, builds her support networks, and discovers resources for adolescents aging out of the foster care system via her work with Dr. Williams, creator and counselor of the Students That Are Reaching Success (S.T.A.R.S.) program. Results from Rose's participation in the program will be shared and implications for counselors working with adolescents aging out of the foster care system will be reviewed.


2020 ◽  
Vol 5 (1) ◽  
pp. 17-22
Author(s):  
Ahmad Kailani ◽  
Dina Rafidiyah

Translating an L1 (source text) into a target language would be a daunting task and time-consuming work for students who are non-native speakers. It might be more challenging when the L1 text is a discipline specific text. Many words and specific terms are difficult to translate, and often unintended meanings emerge during this translation process. Although there has been considerable research on the translation studies, there has been still little study on how translators cope with the challenges. To fill this void, this case study is aimed to describe techniques employed by students majoring pharmacy in translating direction for use texts from English into Bahasa Indonesia. Adopting Vinay’s and Darbelnet’s (1996) translation methodology, this research is aimed to describe the translation process that students already undertook in order to produce texts that appropriately work in a particular social context. There are four drug brochures taken as samples of analysis. These texts are students’ assignment for the topic of translation.  This is a group work and part of the whole assessment. The study provides detailed and specific examples of how students tackle the challenges of translating discipline specific texts into equivalent languages that are socio-culturally and linguistically acceptable. HIGHLIGHTS: Translating a text is not simply to transfer the meaning of source text into the target text, but it requires the translator to have sufficient discipline specific knowledge. The challenges and problems faced by translators would be different from one another since each discipline specific text requires different strategies.


Author(s):  
Rianne Conijn ◽  
Emily Dux Speltz ◽  
Evgeny Chukharev-Hudilainen

AbstractRevision plays an important role in writing, and as revisions break down the linearity of the writing process, they are crucial in describing writing process dynamics. Keystroke logging and analysis have been used to identify revisions made during writing. Previous approaches include the manual annotation of revisions, building nonlinear S-notations, and the automated extraction of backspace keypresses. However, these approaches are time-intensive, vulnerable to construct, or restricted. Therefore, this article presents a computational approach to the automatic extraction of full revision events from keystroke logs, including both insertions and deletions, as well as the characters typed to replace the deleted text. Within this approach, revision candidates are first automatically extracted, which allows for a simplified manual annotation of revision events. Second, machine learning is used to automatically detect revision events. For this, 7120 revision events were manually annotated in a dataset of keystrokes obtained from 65 students conducting a writing task. The results showed that revision events could be automatically predicted with a relatively high accuracy. In addition, a case study proved that this approach could be easily applied to a new dataset. To conclude, computational approaches can be beneficial in providing automated insights into revisions in writing.


Author(s):  
B. Addison ◽  
N. Sarigul-Klijn ◽  
R. Roberto ◽  
A. Jamali ◽  
M. Thompson

This paper presents a high fidelity computational approach to be used in validation of biomechanics experimental measurements. As a demonstration, a case study involving a spinous process implant to correct scoliosis is presented. The biomechanical behavior of the spinous process and implant under tensile loading is investigated using experiments and computations. The experimental study examined the ultimate strength of calf thoracic and lumbar spinous processes in three pullout directions. A statistical analysis was performed on the experimental results to reveal relationships and variations between pullout direction and vertebral type. The finite element high fidelity computational analysis was performed to validate the experimental results. In the process, the material properties of cortical and trabecular bone were elucidated for calf spinous processes. Good comparisons are obtained. The high fidelity computational approach detailed here should serve useful in validation of experimental values from spine biomechanics experimental.


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