scholarly journals Identification of cryptic stator subunits from an apicomplexan ATP synthase

2018 ◽  
Author(s):  
Diego Huet ◽  
Esther Rajendran ◽  
Giel G. Van Dooren ◽  
Sebastian Lourido
Keyword(s):  
Oxygen Consumption ◽  
Atp Synthase ◽  
Hidden Markov ◽  
Mitochondrial Morphology ◽  
Markov Modeling ◽  
Apicomplexan Parasites ◽  
Hidden Markov Modeling ◽  
Mitochondrial Atp Synthase ◽  
Form Part ◽  
Genes Encoding

ABSTRACTThe mitochondrial ATP synthase is a macromolecular motor that uses the proton gradient to generate ATP. Proper ATP synthase function requires a stator linking the catalytic and rotary portions of the complex. However, sequence-based searches fail to identify genes encoding stator subunits in apicomplexan parasites like Toxoplasma gondii or the related organisms that cause malaria. Here, we identify 11 previously unknown subunits from the Toxoplasma ATP synthase, which lack homologs outside the phylum. Hidden Markov modeling suggests that two of them—ICAP2 and ICAP18—share distant homology with mammalian stator subunits. Our analysis shows that both proteins form part of the ATP synthase complex. Depletion of ICAP2 leads to aberrant mitochondrial morphology, decreased oxygen consumption, and disassembly of the complex, consistent with its role as an essential component of the Toxoplasma ATP synthase. Our findings highlight divergent features of the central metabolic machinery in apicomplexans, which may reveal new therapeutic opportunities.

scholarly journals Identification of cryptic subunits from an apicomplexan ATP synthase

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Diego Huet ◽  
Esther Rajendran ◽  
Giel G van Dooren ◽  
Sebastian Lourido
Keyword(s):  
Oxygen Consumption ◽  
Toxoplasma Gondii ◽  
Atp Synthase ◽  
Proton Gradient ◽  
Mitochondrial Morphology ◽  
Apicomplexan Parasites ◽  
Essential Component ◽  
Mitochondrial Atp Synthase ◽  
Form Part ◽  
Genes Encoding

The mitochondrial ATP synthase is a macromolecular motor that uses the proton gradient to generate ATP. Proper ATP synthase function requires a stator linking the catalytic and rotary portions of the complex. However, sequence-based searches fail to identify genes encoding stator subunits in apicomplexan parasites like Toxoplasma gondii or the related organisms that cause malaria. Here, we identify 11 previously unknown subunits from the Toxoplasma ATP synthase, which lack homologs outside the phylum. Modeling suggests that two of them, ICAP2 and ICAP18, are distantly related to mammalian stator subunits. Our analysis shows that both proteins form part of the ATP synthase complex. Depletion of ICAP2 leads to aberrant mitochondrial morphology, decreased oxygen consumption, and disassembly of the complex, consistent with its role as an essential component of the Toxoplasma ATP synthase. Our findings highlight divergent features of the central metabolic machinery in apicomplexans, which may reveal new therapeutic opportunities.

Deriving Effective Decision-Making Strategies of Prosthetists: Using Hidden Markov Modeling and Qualitative Analysis to Compare Experts and Novices

2021 ◽  
pp. 001872082110328
Author(s):  
Pratima Saravanan ◽  
Jessica Menold
Keyword(s):  
Decision Making ◽  
Qualitative Analysis ◽  
Clinical Decision Making ◽  
Hidden Markov ◽  
Activity Level ◽  
Markov Modeling ◽  
Support Tool ◽  
Case Complexity ◽  
Hidden Markov Modeling ◽  
Expert And Novice

Objective This research focuses on studying the clinical decision-making strategies of expert and novice prosthetists for different case complexities. Background With an increasing global amputee population, there is an urgent need for improved amputee care. However, current prosthetic prescription standards are based on subjective expertise, making the process challenging for novices, specifically during complex patient cases. Hence, there is a need for studying the decision-making strategies of prosthetists. Method An interactive web-based survey was developed with two case studies of varying complexities. Navigation between survey pages and time spent were recorded for 28 participants including experts ( n = 20) and novices ( n = 8). Using these data, decision-making strategies, or patterns of decisions, during prosthetic prescription were derived using hidden Markov modeling. A qualitative analysis of participants’ rationale regarding decisions was used to add a deep contextualized understanding of decision-making strategies derived from the quantitative analysis. Results Unique decision-making strategies were observed across expert and novice participants. Experts tended to focus on the personal details, activity level, and state of the residual limb prior to prescription, and this strategy was independent of case complexity. Novices tended to change strategies dependent upon case complexity, fixating on certain factors when case complexity was high. Conclusion The decision-making strategies of experts stayed the same across the two cases, whereas the novices exhibited mixed strategies. Application By modeling the decision-making strategies of experts and novices, this study builds a foundation for development of an automated decision-support tool for prosthetic prescription, advancing novice training, and amputee care.

scholarly journals The ATP Synthase Deficiency in Human Diseases

Life ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 325
Author(s):  
Chiara Galber ◽  
Stefania Carissimi ◽  
Alessandra Baracca ◽  
Valentina Giorgio
Keyword(s):  
Oxidative Phosphorylation ◽  
Atp Synthase ◽  
Mitochondrial Protein ◽  
High Energy ◽  
Neurocognitive Disorders ◽  
Human Diseases ◽  
Age Related ◽  
Muscle Tissues ◽  
Mitochondrial Atp Synthase ◽  
Genes Encoding

Human diseases range from gene-associated to gene-non-associated disorders, including age-related diseases, neurodegenerative, neuromuscular, cardiovascular, diabetic diseases, neurocognitive disorders and cancer. Mitochondria participate to the cascades of pathogenic events leading to the onset and progression of these diseases independently of their association to mutations of genes encoding mitochondrial protein. Under physiological conditions, the mitochondrial ATP synthase provides the most energy of the cell via the oxidative phosphorylation. Alterations of oxidative phosphorylation mainly affect the tissues characterized by a high-energy metabolism, such as nervous, cardiac and skeletal muscle tissues. In this review, we focus on human diseases caused by altered expressions of ATP synthase genes of both mitochondrial and nuclear origin. Moreover, we describe the contribution of ATP synthase to the pathophysiological mechanisms of other human diseases such as cardiovascular, neurodegenerative diseases or neurocognitive disorders.

Decision-Feedback Stages Revealed by Hidden Markov Modeling of EEG

2021 ◽  
pp. 2150031
Author(s):  
Qin Tao ◽  
Yajing Si ◽  
Fali Li ◽  
Peiyang Li ◽  
Yuqin Li ◽  
...  
Keyword(s):  
Frontal Lobe ◽  
Visual Information ◽  
Hidden Markov ◽  
Decision Feedback ◽  
Markov Modeling ◽  
Feedback Process ◽  
Feedback Systems ◽  
Left Frontal Lobe ◽  
Hidden Markov Modeling ◽  
Independent Decision

Decision response and feedback in gambling are interrelated. Different decisions lead to different ranges of feedback, which in turn influences subsequent decisions. However, the mechanism underlying the continuous decision-feedback process is still left unveiled. To fulfill this gap, we applied the hidden Markov model (HMM) to the gambling electroencephalogram (EEG) data to characterize the dynamics of this process. Furthermore, we explored the differences between distinct decision responses (i.e. choose large or small bets) or distinct feedback (i.e. win or loss outcomes) in corresponding phases. We demonstrated that the processing stages in decision-feedback process including strategy adjustment and visual information processing can be characterized by distinct brain networks. Moreover, time-varying networks showed, after decision response, large bet recruited more resources from right frontal and right center cortices while small bet was more related to the activation of the left frontal lobe. Concerning feedback, networks of win feedback showed a strong right frontal and right center pattern, while an information flow originating from the left frontal lobe to the middle frontal lobe was observed in loss feedback. Taken together, these findings shed light on general principles of natural decision-feedback and may contribute to the design of biologically inspired, participant-independent decision-feedback systems.

Sign in / Sign up

Export Citation Format

Share Document