PeerJ Preprints: Biophysicshttps://peerj.com/preprints/index.atom?journal=peerj&subject=600Biophysics articles published in PeerJ PreprintsThe investigation of 2D monolayers as potential chelation agents in Alzheimer’s diseasehttps://peerj.com/preprints/279422019-11-202019-11-20Neha PavuluruXuan Luo
In this study, we conducted Density Functional Theory calculations comparing the binding energy of the copper- Amyloid-beta complex to the binding energies of potential chelation materials. We used the first-coordination sphere of the truncated high-pH Amyloid-beta protein subject to computational limits. Binding energy and charge transfer calculations were evaluated for copper’s interaction with potential chelators: monolayer boron nitride, monolayer molybdenum disulfide, and monolayer silicene. Silicene produced the highest binding energies to copper, and the evidence of charge transfer between copper and the monolayer proves that there is a strong ionic bond present. Although our three monolayers did not directly present chelation potential, the absolute differences between the binding energies of the silicene binding sites and the Amyloid-beta binding site were minimal proving that further research in silicene chelators may be useful for therapy in Alzheimer’s disease.
In this study, we conducted Density Functional Theory calculations comparing the binding energy of the copper- Amyloid-beta complex to the binding energies of potential chelation materials. We used the first-coordination sphere of the truncated high-pH Amyloid-beta protein subject to computational limits. Binding energy and charge transfer calculations were evaluated for copper’s interaction with potential chelators: monolayer boron nitride, monolayer molybdenum disulfide, and monolayer silicene. Silicene produced the highest binding energies to copper, and the evidence of charge transfer between copper and the monolayer proves that there is a strong ionic bond present. Although our three monolayers did not directly present chelation potential, the absolute differences between the binding energies of the silicene binding sites and the Amyloid-beta binding site were minimal proving that further research in silicene chelators may be useful for therapy in Alzheimer’s disease.Wave propagation in the biosonar organ of sperm whales using a finite difference time domain methodhttps://peerj.com/preprints/279952019-09-302019-09-30Maxence FerrariRicard MarxerMark AschHervé Glotin
The bio-sonar of sperm whales presents many specific characteristics, such as its size, its loudness or its vocalization abilities. Furthermore it fulfills several roles in their foraging and social behaviour. However our knowledge about its operation remains limited to the main acoustic path that the emitted pulse may take. We still ignore the precise mechanisms that shape the wave and on which parts the sperm whale is able to act. In this paper, we describe a technique to simulate sperm whale click generation from a physical perspective. Such an approach aims at unveiling the processes involved in their vocal production, as a stepping stone towards a better understanding of their interaction with peers and the environment.
The bio-sonar of sperm whales presents many specific characteristics, such as its size, its loudness or its vocalization abilities. Furthermore it fulfills several roles in their foraging and social behaviour. However our knowledge about its operation remains limited to the main acoustic path that the emitted pulse may take. We still ignore the precise mechanisms that shape the wave and on which parts the sperm whale is able to act. In this paper, we describe a technique to simulate sperm whale click generation from a physical perspective. Such an approach aims at unveiling the processes involved in their vocal production, as a stepping stone towards a better understanding of their interaction with peers and the environment.KCNMA1-linked channelopathyhttps://peerj.com/preprints/278762019-08-192019-08-19Cole S BaileyHans J MoldenhauerSu Mi ParkSotirios KerosAndrea L Meredith
KCNMA1 encodes the pore-forming α subunit of the ‘Big K+’ (BK) large conductance calcium and voltage-activated K+ channel. BK channels are widely distributed across tissues, including both excitable and non-excitable cells. Expression levels are highest in brain and muscle, where BK channels are critical regulators of neuronal excitability and muscle contractility. A global deletion in mouse (KCNMA1–/–) is viable but exhibits pathophysiology in many organ systems. Yet despite the important roles in animal models, the consequences of dysfunctional BK channels in humans are not well-characterized. Here, we summarize 16 rare KCNMA1 mutations identified in 37 patients dating back to 2005, with an array of clinically defined pathological phenotypes collectively referred to as ‘KCNMA1-linked channelopathy.’ These mutations encompass gain-of-function (GOF) and loss-of-function (LOF) alterations in BK channel activity, as well as several variants of unknown significance (VUS). Human KCNMA1 mutations are primarily associated with neurological conditions, including seizures, movement disorders, developmental delay, and intellectual disability. Due to the recent identification of additional patients, the spectrum of symptoms associated with KCNMA1 mutations has expanded but remains primarily defined by brain and muscle dysfunction. Emerging evidence suggests the functional BK channel alterations produced by different KCNMA1 alleles may associate with semi-distinct patient symptoms, such as paroxysmal non-kinesigenic dyskinesia (PNKD) with GOF and ataxia with LOF. However, due to the de novo origins for the majority of KCNMA1 mutations identified to date, and the phenotypic variability exhibited by patients, additional evidence is required to establish causality in most cases. The symptomatic picture developing from patients with KCNMA1-linked channelopathy highlights the importance of better understanding the roles BK channels play in regulating cell excitability. Establishing causality between KCNMA1-linked BK channel dysfunction and specific patient symptoms may reveal new treatment approaches with the potential to increase therapeutic efficacy over current standard regimens.
KCNMA1 encodes the pore-forming α subunit of the ‘Big K+’ (BK) large conductance calcium and voltage-activated K+ channel. BK channels are widely distributed across tissues, including both excitable and non-excitable cells. Expression levels are highest in brain and muscle, where BK channels are critical regulators of neuronal excitability and muscle contractility. A global deletion in mouse (KCNMA1–/–) is viable but exhibits pathophysiology in many organ systems. Yet despite the important roles in animal models, the consequences of dysfunctional BK channels in humans are not well-characterized. Here, we summarize 16 rare KCNMA1 mutations identified in 37 patients dating back to 2005, with an array of clinically defined pathological phenotypes collectively referred to as ‘KCNMA1-linked channelopathy.’ These mutations encompass gain-of-function (GOF) and loss-of-function (LOF) alterations in BK channel activity, as well as several variants of unknown significance (VUS). Human KCNMA1 mutations are primarily associated with neurological conditions, including seizures, movement disorders, developmental delay, and intellectual disability. Due to the recent identification of additional patients, the spectrum of symptoms associated with KCNMA1 mutations has expanded but remains primarily defined by brain and muscle dysfunction. Emerging evidence suggests the functional BK channel alterations produced by different KCNMA1 alleles may associate with semi-distinct patient symptoms, such as paroxysmal non-kinesigenic dyskinesia (PNKD) with GOF and ataxia with LOF. However, due to the de novo origins for the majority of KCNMA1 mutations identified to date, and the phenotypic variability exhibited by patients, additional evidence is required to establish causality in most cases. The symptomatic picture developing from patients with KCNMA1-linked channelopathy highlights the importance of better understanding the roles BK channels play in regulating cell excitability. Establishing causality between KCNMA1-linked BK channel dysfunction and specific patient symptoms may reveal new treatment approaches with the potential to increase therapeutic efficacy over current standard regimens.Designing a bioremediator: mechanistic models guide cellular and molecular specializationhttps://peerj.com/preprints/278382019-07-032019-07-03Marco ZaccariaWilliam DawsonViviana CristiglioMassimo ReverberiLaura E. RatcliffTakahito NakajimaLuigi GenoveseBabak Momeni
Rational, mechanistic design can substantially improve the performance of bioremediators for applications including waste treatment and food safety. We highlight how such improvement can be informed at the cellular level by theoretical observations especially in the context of phenotype plasticity, cell signaling, and community assembly. At the molecular level, we suggest enzyme design using techniques such as Small Angle Neutron Scattering and Density Functional Theory. To provide an example of how these techniques could be synergistically combined, we present the case-study of the interaction of the enzyme laccase with the food pollutant aflatoxin B1. In designing bioremediators, we encourage interdisciplinary, mechanistic research to transition from an observation-oriented approach to a principle-based one.
Rational, mechanistic design can substantially improve the performance of bioremediators for applications including waste treatment and food safety. We highlight how such improvement can be informed at the cellular level by theoretical observations especially in the context of phenotype plasticity, cell signaling, and community assembly. At the molecular level, we suggest enzyme design using techniques such as Small Angle Neutron Scattering and Density Functional Theory. To provide an example of how these techniques could be synergistically combined, we present the case-study of the interaction of the enzyme laccase with the food pollutant aflatoxin B1. In designing bioremediators, we encourage interdisciplinary, mechanistic research to transition from an observation-oriented approach to a principle-based one.Bacterial Type VI secretion system could have evolved from co-opted tail sheath tube of bacteriophageshttps://peerj.com/preprints/276522019-04-152019-04-15Wenfa Ng
Bacterial cells utilize a variety of nanomachines to secrete proteins and other molecules into the extracellular environment or target cells. One example is the Type VI secretion system (T6SS) in Gram-negative bacteria. Armed with a contractile mechanism similar to that used by bacteriophages to inject phage DNA into bacterial cells, the T6SS shares a common evolutionary origin with tail associated proteins of bacteriophages at both the structural and protein composition levels. Specifically, proteins constituting the T6SS are known to share provenance with those of the phage tail protein. More importantly, the T6SS is strikingly similar to the phage tail protein in both structure and function. However, a more important question concerns whether the T6SS evolved from the phage tail protein and if yes, what is the mechanism responsible for its development? One possibility could be the co-opt of the tail protein structure by bacterial cells through integration of the genes encoding the tail protein structure within the bacterial genome. In this case, expression of the phage tail protein genes would have resulted in a multiprotein structure without apparent function, which meant that a significant gap remains in comparison with extant T6SS that spans the inner and outer cell membrane of Gram-negative bacteria. While it is desirable to trace the evolutionary steps taken by phage tail proteins to transform into functional T6SS, multiple selection pressure and strong mutational propensity might have erased molecular evidence of such transformation. Hence, the challenge lies in uncovering as much structural and sequence evidence as possible that points to distinct steps in the evolutionary pathway towards T6SS. Structural studies offer a particularly promising route to unentangle the details but it must be augmented with sequence evidence that pins down the molecular events that shape the evolution of the complex multiprotein structure, where clefts from one protein fit into the folds of another in yielding a function that could evolve over eons. Collectively, structural and functional similarity between T6SS and phage tail protein suggests a common evolutionary origin for both macromolecular complexes, which has been established through combined structural, compositional and sequence analysis. But the steps underpinning the transformation of phage tail protein into T6SS remain unclear, which obfuscate understanding of the evolutionary forces that shape the transformation. One possible evolutionary trajectory posits that genes expressing phage tail proteins were co-opted and integrated into the bacterial genome. However, significant gap remains between a phage tail protein structure with unclear function in the cytoplasm and a functional T6SS that spans two bacterial membranes. Future detective work at the structural and sequence level might offer clues to the evolutionary path trodden by a precursor of the bacterial T6SS.
Bacterial cells utilize a variety of nanomachines to secrete proteins and other molecules into the extracellular environment or target cells. One example is the Type VI secretion system (T6SS) in Gram-negative bacteria. Armed with a contractile mechanism similar to that used by bacteriophages to inject phage DNA into bacterial cells, the T6SS shares a common evolutionary origin with tail associated proteins of bacteriophages at both the structural and protein composition levels. Specifically, proteins constituting the T6SS are known to share provenance with those of the phage tail protein. More importantly, the T6SS is strikingly similar to the phage tail protein in both structure and function. However, a more important question concerns whether the T6SS evolved from the phage tail protein and if yes, what is the mechanism responsible for its development? One possibility could be the co-opt of the tail protein structure by bacterial cells through integration of the genes encoding the tail protein structure within the bacterial genome. In this case, expression of the phage tail protein genes would have resulted in a multiprotein structure without apparent function, which meant that a significant gap remains in comparison with extant T6SS that spans the inner and outer cell membrane of Gram-negative bacteria. While it is desirable to trace the evolutionary steps taken by phage tail proteins to transform into functional T6SS, multiple selection pressure and strong mutational propensity might have erased molecular evidence of such transformation. Hence, the challenge lies in uncovering as much structural and sequence evidence as possible that points to distinct steps in the evolutionary pathway towards T6SS. Structural studies offer a particularly promising route to unentangle the details but it must be augmented with sequence evidence that pins down the molecular events that shape the evolution of the complex multiprotein structure, where clefts from one protein fit into the folds of another in yielding a function that could evolve over eons. Collectively, structural and functional similarity between T6SS and phage tail protein suggests a common evolutionary origin for both macromolecular complexes, which has been established through combined structural, compositional and sequence analysis. But the steps underpinning the transformation of phage tail protein into T6SS remain unclear, which obfuscate understanding of the evolutionary forces that shape the transformation. One possible evolutionary trajectory posits that genes expressing phage tail proteins were co-opted and integrated into the bacterial genome. However, significant gap remains between a phage tail protein structure with unclear function in the cytoplasm and a functional T6SS that spans two bacterial membranes. Future detective work at the structural and sequence level might offer clues to the evolutionary path trodden by a precursor of the bacterial T6SS.Structural basis of response regulator functionhttps://peerj.com/preprints/275542019-03-212019-03-21Rong GaoSophie BouilletAnn Stock
Response regulators function as the output components of two-component systems, which couple the sensing of environmental stimuli to adaptive responses. Response regulators typically contain conserved receiver (REC) domains that function as phosphorylation-regulated switches to control the activities of effector domains that elicit output responses. This modular design is extremely versatile, enabling different regulatory strategies tuned to the needs of individual signaling systems. This review summarizes functional features that underlie response regulator function. An abundance of atomic resolution structures and complementary biochemical data have defined the mechanisms for response regulator enzymatic activities, revealed trends in regulatory strategies utilized by response regulators of different subfamilies and provided insights into interactions of response regulators with their cognate histidine kinases. Among the hundreds of thousands of response regulators identified, variations abound. This article provides a framework for understanding structural features that enable function of canonical response regulators and a basis for distinguishing non-canonical configurations.
Response regulators function as the output components of two-component systems, which couple the sensing of environmental stimuli to adaptive responses. Response regulators typically contain conserved receiver (REC) domains that function as phosphorylation-regulated switches to control the activities of effector domains that elicit output responses. This modular design is extremely versatile, enabling different regulatory strategies tuned to the needs of individual signaling systems. This review summarizes functional features that underlie response regulator function. An abundance of atomic resolution structures and complementary biochemical data have defined the mechanisms for response regulator enzymatic activities, revealed trends in regulatory strategies utilized by response regulators of different subfamilies and provided insights into interactions of response regulators with their cognate histidine kinases. Among the hundreds of thousands of response regulators identified, variations abound. This article provides a framework for understanding structural features that enable function of canonical response regulators and a basis for distinguishing non-canonical configurations.Using 3D micro-geomorphometry to quantify interstitial spaces of an oyster clusterhttps://peerj.com/preprints/275962019-03-182019-03-18Kwanmok KimVincent LecoursPeter C. Frederick
In ecology, it is assumed that the characteristics (e.g. shape, size) of interstitial spaces found in a variety of habitats affect the colonization of species, species interactions, and species composition. However, those characteristics have traditionally been difficult to measure due to technological limitations. In this study, we used the Structure-from-Motion (SfM) photogrammetry technique to measure the physical characteristics of interstitial spaces in a small oyster cluster. The point cloud (and mesh) of the oyster cluster derived from SfM photogrammetry was found to be accurate enough (mean error of 0.654 mm) to conduct 3D geomorphometric analyses. We present an example of measures of curvature, roughness, interstitial volume, surface area, and openness for three 3D interstitial spaces. The interpretation of those measures enabled establishing which interstitial spaces were the most likely to be used as a shelter for an average crab. Those spaces are characterized by smaller openness and higher roughness and curvature measures. This initial quantitative 3D characterization of an oyster cluster is the first step in establishing empirical relationships between structural complexity of biological structures like oyster clusters and their ecological role for instance in predator-prey interactions. Overall, this study demonstrates the feasibility of combining SfM photogrammetry with geomorphometry for fine-scale ecological studies.
In ecology, it is assumed that the characteristics (e.g. shape, size) of interstitial spaces found in a variety of habitats affect the colonization of species, species interactions, and species composition. However, those characteristics have traditionally been difficult to measure due to technological limitations. In this study, we used the Structure-from-Motion (SfM) photogrammetry technique to measure the physical characteristics of interstitial spaces in a small oyster cluster. The point cloud (and mesh) of the oyster cluster derived from SfM photogrammetry was found to be accurate enough (mean error of 0.654 mm) to conduct 3D geomorphometric analyses. We present an example of measures of curvature, roughness, interstitial volume, surface area, and openness for three 3D interstitial spaces. The interpretation of those measures enabled establishing which interstitial spaces were the most likely to be used as a shelter for an average crab. Those spaces are characterized by smaller openness and higher roughness and curvature measures. This initial quantitative 3D characterization of an oyster cluster is the first step in establishing empirical relationships between structural complexity of biological structures like oyster clusters and their ecological role for instance in predator-prey interactions. Overall, this study demonstrates the feasibility of combining SfM photogrammetry with geomorphometry for fine-scale ecological studies.Adaptation of gestation or egg-laying in species depends on the amount of internal heat generated in digesting the foodhttps://peerj.com/preprints/274602019-02-192019-02-19Karunakar Marasakatla
Anatomically and physiologically, the reproductive process of gestation or egg-laying, and dietary habits in vertebrates appear to be distinct processes. An in-depth analysis of the dietary habits of vertebrates reveals that the gestation or egg-laying characteristic in these species is tightly coupled with the digestive process. Once the food has been ingested, it is then broken down to the molecular level to be absorbed into the body. The amount of energy required to digest the food depends upon the amount and composition of the food material that was ingested. The denser (ex. bones and muscle) and bigger the size of the food bits ingested, the higher the amount of energy required to break down the material - that in turn requires higher amount of gastrointestinal acids. Where there is higher amount of energy is consumed, there will be an excess amount of heat gets generated. Because of the proximity of uterus to digestive system, a layer develops around the embryo to protect it from this heat. Therefore, it appears that the higher amount of heat generated in digesting the food results in egg-laying characteristic in species such as birds and reptiles, which ingest large chunks of raw meat. Rest of the vertebrates adapted to gestation due to chewing the food into small pieces before ingesting which generates less internal heat in digestion. Species, which generate higher amount of internal heat in digestion, adapted to ectothermic nature such as reptiles. And the species, which generate less amount of internal heat, adapted to endothermic nature such as mammals. Birds are endothermic but they would have been ectothermic if there were no insulating feathers.
Anatomically and physiologically, the reproductive process of gestation or egg-laying, and dietary habits in vertebrates appear to be distinct processes. An in-depth analysis of the dietary habits of vertebrates reveals that the gestation or egg-laying characteristic in these species is tightly coupled with the digestive process. Once the food has been ingested, it is then broken down to the molecular level to be absorbed into the body. The amount of energy required to digest the food depends upon the amount and composition of the food material that was ingested. The denser (ex. bones and muscle) and bigger the size of the food bits ingested, the higher the amount of energy required to break down the material - that in turn requires higher amount of gastrointestinal acids. Where there is higher amount of energy is consumed, there will be an excess amount of heat gets generated. Because of the proximity of uterus to digestive system, a layer develops around the embryo to protect it from this heat. Therefore, it appears that the higher amount of heat generated in digesting the food results in egg-laying characteristic in species such as birds and reptiles, which ingest large chunks of raw meat. Rest of the vertebrates adapted to gestation due to chewing the food into small pieces before ingesting which generates less internal heat in digestion. Species, which generate higher amount of internal heat in digestion, adapted to ectothermic nature such as reptiles. And the species, which generate less amount of internal heat, adapted to endothermic nature such as mammals. Birds are endothermic but they would have been ectothermic if there were no insulating feathers.Ellipse packing in two-dimensional celltessellation: A theoretical explanation for Lewis’s law and Aboav-Weaire’s lawhttps://peerj.com/preprints/274212019-02-012019-02-01Kai Xu
Background: Lewis’s law and Aboav-Weaire’s law are two fundamental laws used to describe the topology of two-dimensional (2D) structures; however, their theoretical bases remain unclear.
Methods: We used R package Conicfit software to fit ellipses based on the geometric parameters of polygonal cells with ten different kinds of natural and artificial 2D structures.
Results: Our results indicated that the cells could be classified as ellipse’s inscribed polygon (EIP) and that they tended to form ellipse’s maximal inscribed polygon (EMIP). This phenomenon was named as ellipse packing. On the basis of the number of cell edges, cell area, and semi-axes of fitted ellipses, we derived and verified new relations of Lewis’s law and Aboav-Weaire’s law .
Conclusions: Ellipse packing is a short-range order that places restrictions on the cell topology and growth pattern. Lewis’s law and Aboav-Weaire’s law mainly reflect the effect of deformation from circle to ellipse on cell area and the edge number of neighboring cells, respectively. The results of this study could be used to simulate the dynamics of cell topology during growth.
Background: Lewis’s law and Aboav-Weaire’s law are two fundamental laws used to describe the topology of two-dimensional (2D) structures; however, theirtheoretical bases remain unclear. Methods: We used R package Conicfit software to fit ellipses based on the geometric parameters of polygonal cells with ten different kinds of natural and artificial 2D structures. Results: Our results indicated that the cells could be classified as ellipse’s inscribed polygon (EIP) and that they tended to form ellipse’s maximal inscribed polygon (EMIP). This phenomenon was named as ellipse packing. On the basis of the number of cell edges, cell area, and semi-axes of fitted ellipses, we derived and verified new relations of Lewis’s law and Aboav-Weaire’s law . Conclusions: Ellipse packing is a short-range order that places restrictions on the cell topology and growth pattern. Lewis’s law and Aboav-Weaire’s law mainly reflect the effect of deformation from circle to ellipse on cell area and the edge number of neighboring cells, respectively. The results of this study could be used to simulate the dynamics of cell topology during growth.The extreme degeneracy of inputs in firing a neuron leads to loss of information when neuronal firing is examinedhttps://peerj.com/preprints/272282019-01-192019-01-19Kunjumon I Vadakkan
Possible combinations of inputs in the order of 10100 can fire (axonal spike or action potential) a neuron that has nearly 104 inputs (dendritic spines). This extreme degeneracy of inputs that can fire a neuron is associated with significant loss of information when examination is limited to neuronal firing. Excitatory postsynaptic potentials (EPSPs) propagating from remote locations on the dendritic tree attenuate as they arrive at the axon hillock, depending on the distance they propagate. Moreover, some EPSPs from remote locations will not even reach the axonal hillock. In this context, an operational mechanism at the location of origin of these EPSPs is necessary to preserve information for efficient storage. Evidence for information storage or retrieval can be observed only as the tip of an iceberg of operational mechanisms occurring at a narrow window when sub-threshold activated (before learning) neurons fire during these events. Even firing of a set of neurons does not identify the location where information is stored due to the extreme degeneracy of inputs that can contribute potentials to cross the threshold and fire those neurons. In summary, it is necessary to identify initial locations where specific inputs to a neuron arrive where information is expected to make retrieval-efficient changes.
Possible combinations of inputs in the order of 10100 can fire (axonal spike or action potential) a neuron that has nearly 104 inputs (dendritic spines). This extreme degeneracy of inputs that can fire a neuron is associated with significant loss of information when examination is limited to neuronal firing. Excitatory postsynaptic potentials (EPSPs) propagating from remote locations on the dendritic tree attenuate as they arrive at the axon hillock, depending on the distance they propagate. Moreover, some EPSPs from remote locations will not even reach the axonal hillock. In this context, an operational mechanism at the location of origin of these EPSPs is necessary to preserve information for efficient storage. Evidence for information storage or retrieval can be observed only as the tip of an iceberg of operational mechanisms occurring at a narrow window when sub-threshold activated (before learning) neurons fire during these events. Even firing of a set of neurons does not identify the location where information is stored due to the extreme degeneracy of inputs that can contribute potentials to cross the threshold and fire those neurons. In summary, it is necessary to identify initial locations where specific inputs to a neuron arrive where information is expected to make retrieval-efficient changes.