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https://www.readbyqxmd.com/read/29145393/estimating-the-probabilities-of-rare-arrhythmic-events-in-multiscale-computational-models-of-cardiac-cells-and-tissue
#1
Mark A Walker, Viatcheslav Gurev, John J Rice, Joseph L Greenstein, Raimond L Winslow
Ectopic heartbeats can trigger reentrant arrhythmias, leading to ventricular fibrillation and sudden cardiac death. Such events have been attributed to perturbed Ca2+ handling in cardiac myocytes leading to spontaneous Ca2+ release and delayed afterdepolarizations (DADs). However, the ways in which perturbation of specific molecular mechanisms alters the probability of ectopic beats is not understood. We present a multiscale model of cardiac tissue incorporating a biophysically detailed three-dimensional model of the ventricular myocyte...
November 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/29129207/fusion-pore-in-exocytosis-more-than-an-exit-gate-a-%C3%AE-cell-perspective
#2
REVIEW
Benoit Hastoy, Anne Clark, Patrik Rorsman, Jochen Lang
Secretory vesicle exocytosis is a fundamental biological event and the process by which hormones (like insulin) are released into the blood. Considerable progress has been made in understanding this precisely orchestrated sequence of events from secretory vesicle docked at the cell membrane, hemifusion, to the opening of a membrane fusion pore. The exact biophysical and physiological regulation of these events implies a close interaction between membrane proteins and lipids in a confined space and constrained geometry to ensure appropriate delivery of cargo...
December 2017: Cell Calcium
https://www.readbyqxmd.com/read/29124054/a-method-for-the-analysis-of-ap-foot-convexity-insights-into-smooth-muscle-biophysics
#3
Shailesh Appukuttan, Mithun Padmakumar, Keith L Brain, Rohit Manchanda
Action potential (AP) profiles vary based on the cell type, with cells of the same type typically producing APs with similar shapes. But in certain syncytial tissues, such as the smooth muscle of the urinary bladder wall, even a single cell is known to exhibit APs with diverse profiles. The origin of this diversity is not currently understood, but is often attributed to factors such as syncytial interactions and the spatial distribution of parasympathetic nerve terminals. Thus, the profile of an action potential is determined by the inherent properties of the cell and influenced by its biophysical environment...
2017: Frontiers in Bioengineering and Biotechnology
https://www.readbyqxmd.com/read/29122925/genetic-circuit-characterization-and-debugging-using-rna-seq
#4
Thomas E Gorochowski, Amin Espah Borujeni, Yongjin Park, Alec Ak Nielsen, Jing Zhang, Bryan S Der, D Benjamin Gordon, Christopher A Voigt
Genetic circuits implement computational operations within a cell. Debugging them is difficult because their function is defined by multiple states (e.g., combinations of inputs) that vary in time. Here, we develop RNA-seq methods that enable the simultaneous measurement of: (i) the states of internal gates, (ii) part performance (promoters, insulators, terminators), and (iii) impact on host gene expression. This is applied to a three-input one-output circuit consisting of three sensors, five NOR/NOT gates, and 46 genetic parts...
November 9, 2017: Molecular Systems Biology
https://www.readbyqxmd.com/read/29121574/in-vitro-interaction-of-cefotaxime-with-calf-thymus-dna-insights-from-spectroscopic-calorimetric-and-molecular-modelling-studies
#5
Faizan Abul Qais, Iqbal Ahmad
Cefotaxime is third generation antibiotic with known therapeutic efficacy against bacterial infections including cerebral abscesses and bacterial meningitis. The β-lactam group of drugs are considered safest antibiotics. Many antibiotics directly interact with DNA and alter their expression profile. Thus, it is necessary to understand the binding mode and its relevance to drug activity and toxicity. There is considerably a remarkable focus on deciphering the binding mechanism of these therapeutic agents as DNA is one of the major target for wide range of drugs...
October 28, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29113034/directed-evolution-of-recombinant-c-terminal-truncated-staphylococcus-epidermidis-lipase-at2-for-the-enhancement-of-thermostability
#6
Jiivittha Veno, Nor Hafizah Ahmad Kamarudin, Mohd Shukuri Mohamad Ali, Malihe Masomian, Raja Noor Zaliha Raja Abd Rahman
In the industrial processes, lipases are expected to operate at temperatures above 45 °C and could retain activity in organic solvents. Hence, a C-terminal truncated lipase from Staphylococcus epidermis AT2 (rT-M386) was engineered by directed evolution. A mutant with glycine-to-cysteine substitution (G210C) demonstrated a remarkable improvement of thermostability, whereby the mutation enhanced the activity five-fold when compared to the rT-M386 at 50 °C. The rT-M386 and G210C lipases were purified concurrently using GST-affinity chromatography...
November 4, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29069587/biophysical-variation-within-the-m1-type-of-ganglion-cell-photoreceptor
#7
Alan J Emanuel, Kush Kapur, Michael Tri H Do
Intrinsically photosensitive retinal ganglion cells of the M1 type encode environmental irradiance for functions that include circadian and pupillary regulation. Their distinct role, morphology, and molecular markers indicate that they are stereotyped circuit elements, but their physiological uniformity has not been investigated in a systematic fashion. We have profiled the biophysical parameters of mouse M1s and found that extreme variation is their hallmark. Most parameters span 1-3 log units, and the full range is evident in M1s that innervate brain regions serving divergent functions...
October 24, 2017: Cell Reports
https://www.readbyqxmd.com/read/29064795/the-impact-of-emergent-infections-on-the-fetal-state
#8
Liudmyla A Vygivska, Iryna O Tuchkina, Violetta B Kalnytska
THE AIM: To study the impact of emergent infections (human herpesvirus type 6) on the fetal state. MATERIALS AND METHODS: The study involved examination of 90 pregnant women in the 2nd and 3rd trimesters of gestation (Group 1 (25 pregnant) consisted of patients with a viral infection, CMV carriers, Group 2 (25 pregnant) included women with a viral infection, herpes simplex virus types 1/2, Group 3 amounted for 20 patients with a viral infection, herpes simplex virus type 6, Group 4 comprised 20 patients with normal pregnancy and no signs of infection...
2017: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/29061904/chlorophyll-can-be-reduced-in-crop-canopies-with-little-penalty-to-photosynthesis
#9
Berkley J Walker, Darren T Drewry, Rebecca A Slattery, Andy VanLoocke, Young B Cho, Donald R Ort
The hypothesis that reducing chlorophyll content (Chl) can increase canopy photosynthesis in soybeans was tested using an advanced model of canopy photosynthesis. The relationship between leaf Chl, leaf optical properties, and photosynthetic biochemical capacity were measured in 67 soybean accessions showing large variation in leaf Chl. These relationships were integrated into a biophysical model of canopy-scale photosynthesis to simulate the inter-canopy light environment and carbon assimilation capacity of canopies with WT, a Chl-deficient mutant (Y11y11), and 67 other mutants spanning the extremes of Chl to quantify the impact of variation in leaf-level Chl on canopy-scale photosynthetic assimilation and identify possible opportunities for improving canopy photosynthesis through Chl reduction...
October 23, 2017: Plant Physiology
https://www.readbyqxmd.com/read/29040270/analysis-of-the-interaction-of-plexin-b1-and-plexin-b2-with-rnd-family-proteins
#10
Thomas Wylie, Ritu Garg, Anne J Ridley, Maria R Conte
The Rnd family of proteins, Rnd1, Rnd2 and Rnd3, are atypical Rho family GTPases, which bind to but do not hydrolyse GTP. They interact with plexins, which are receptors for semaphorins, and are hypothesised to regulate plexin signalling. We recently showed that each Rnd protein has a distinct profile of interaction with three plexins, Plexin-B1, Plexin-B2 and Plexin-B3, in mammalian cells, although it is unclear which region(s) of these plexins contribute to this specificity. Here we characterise the binary interactions of the Rnd proteins with the Rho-binding domain (RBD) of Plexin-B1 and Plexin-B2 using biophysical approaches...
2017: PloS One
https://www.readbyqxmd.com/read/29028292/dynamics-of-soil-biogeochemical-gas-emissions-shaped-by-remolded-aggregate-sizes-and-carbon-configurations-under-hydration-cycles
#11
Ali Ebrahimi, Dani Or
Changes in soil hydration status affect microbial community dynamics and shape key biogeochemical processes. Evidence suggests that local anoxic conditions may persist and support anaerobic microbial activity in soil aggregates (or in similar hot spots) long after the bulk soil becomes aerated. To facilitate systematic studies of interactions among environmental factors with biogeochemical emissions of CO2 , N2 O and CH4 from soil aggregates, we remolded silt soil aggregates to different sizes and incorporated carbon at different configurations (core, mixed, no addition)...
October 13, 2017: Global Change Biology
https://www.readbyqxmd.com/read/29026301/rational-design-of-novel-fluorescent-tagged-glutamic-acid-dendrimers-with-different-terminal-groups-and-in-silico-analysis-of-their-properties
#12
Nuno Martinho, Liana C Silva, Helena F Florindo, Steve Brocchini, Mire Zloh, Teresa S Barata
Dendrimers are hyperbranched polymers with a multifunctional architecture that can be tailored for the use in various biomedical applications. Peptide dendrimers are particularly relevant for drug delivery applications due to their versatility and safety profile. The overall lack of knowledge of their three-dimensional structure, conformational behavior and structure-activity relationship has slowed down their development. Fluorophores are often conjugated to dendrimers to study their interaction with biomolecules and provide information about their mechanism of action at the molecular level...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29021157/ribosome-flow-model-with-extended-objects
#13
Yoram Zarai, Michael Margaliot, Tamir Tuller
We study a deterministic mechanistic model for the flow of ribosomes along the mRNA molecule, called the ribosome flow model with extended objects (RFMEO). This model encapsulates many realistic features of translation including non-homogeneous transition rates along mRNA, the fact that every ribosome covers several codons, and the fact that ribosomes cannot overtake one another. The RFMEO is a mean-field approximation of an important model from statistical mechanics called the totally asymmetric simple exclusion process with extended objects (TASEPEO)...
October 2017: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/28981993/membrane-lipid-order-of-sub-synaptic-t-cell-vesicles-correlates-with-their-dynamics-and-function
#14
George W Ashdown, David J Williamson, Gary H M Soh, Nathan Day, Garth L Burn, Dylan M Owen
During an immune response, T cells survey antigen presenting cells for antigenic peptides via the formation of an interface known as an immunological synapse. Among the complex and dynamic biophysical phenomena occurring at this interface is the trafficking of sub-synaptic vesicles carrying a variety of proximal signalling molecules. Here, we show that rather than being a homogeneous population, these vesicles display a diversity of membrane lipid order profiles, as measured using the environmentally sensitive dye di-4-ANEPPDHQ and multi-spectral TIRF microscopy...
October 5, 2017: Traffic
https://www.readbyqxmd.com/read/28973482/high-throughput-characterization-of-the-functional-impact-of-igg-fc-glycan-aberrancy-in-juvenile-idiopathic-arthritis
#15
Hao D Cheng, Henning Stöckmann, Barbara Adamczyk, Ciara A McManus, Altan Ercan, Ingrid A Holm, Pauline M Rudd, Margaret E Ackerman, Peter A Nigrovic
Juvenile idiopathic arthritis (JIA) encompasses all forms of chronic idiopathic arthritis that arise before age 16. Previous studies have found JIA to be associated with lower Fc galactosylation of circulating IgG, but the overall spectrum of glycan changes and the net impact on IgG function are unknown. Using ultra performance liquid chromatography (UPLC), we compared IgG glycosylation in 54 subjects with recent-onset untreated JIA with 98 healthy pediatric controls, paired to biophysical profiling of affinity for 20 IgG receptors using a high-throughput multiplexed microsphere assay...
December 1, 2017: Glycobiology
https://www.readbyqxmd.com/read/28972148/time-course-negative-stain-electron-microscopy-based-analysis-for-investigating-protein-protein-interactions-at-the-single-molecule-level
#16
Bartek Nogal, Charles A Bowman, Andrew B Ward
Several biophysical approaches are available to study protein-protein interactions. Most approaches are conducted in bulk solution, and are therefore limited to an average measurement of the ensemble of molecular interactions. Here, we show how single-particle EM can enrich our understanding of protein-protein interactions at the single-molecule level and potentially capture states that are unobservable with ensemble methods because they are below the limit of detection or not conducted on an appropriate timescale...
September 29, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28971232/terbium-chelation-a-specific-fluorescent-tagging-of-human-transferrin-optimization-of-conditions-in-view-of-its-application-to-the-hplc-analysis-of-carbohydrate-deficient-transferrin-cdt
#17
Silvia Nicotra, Daniela Sorio, Giulia Filippi, Luca De Gioia, Veronica Paterlini, Elio Franco De Palo, Rita Grandori, Franco Tagliaro, Carlo Santambrogio
Transferrin (Tf) is the major iron-transporting protein in the human body and, for this reason, has been extensively studied in biomedicine. This protein undergoes a complex glycosylation process leading to several glycoforms, some of which are important in the diagnosis of alcohol abuse and of congenital glycosylation defects under the collective name of carbohydrate-deficient transferrin (CDT). Exploiting the Tf ability to bind not only iron but also other ions, specific attention has been devoted to binding activity towards Tb(3+), which was reported to greatly enhance its intrinsic fluorescence upon the interaction with Tf...
September 29, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28969216/decreased-foetal-movements-secondary-to-uterine-septum-a-case-report-and-proposed-algorithm-of-management
#18
Eram Ali, Tamkin Khan, Deeba Khanam
Congenital uterine anomaly has been well established as cause of infertility and recurrent pregnancy loss. However, only few studies have reported the association of mullerian anomalies and adverse pregnancy outcome in third trimester. We are hereby reporting a case of 25-year- old female second gravida who presented at 36 weeks six days pregnancy with complaint of decreased foetal movements for the past two weeks. The female had previous history of multiple admissions on account of decreased foetal movements in the third trimester...
August 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28960219/a-bioenergetic-mechanism-for-amoeboid-like-cell-motility-profiles-tested-in-a-microfluidic-electrotaxis-assay
#19
Hagit Peretz-Soroka, Reuven Tirosh, Jolly Hipolito, Erwin Huebner, Murray Alexander, Jason Fiege, Francis Lin
The amoeboid-like cell motility is known to be driven by the acidic enzymatic hydrolysis of ATP in the actin-myosin system. However, the electro-mechano-chemical coupling, whereby the free energy of ATP hydrolysis is transformed into the power of electrically polarized cell movement, is poorly understood. Previous experimental studies showed that actin filaments motion, cytoplasmic streaming, and muscle contraction can be reconstituted under actin-activated ATP hydrolysis by soluble non-filamentous myosin fragments...
November 13, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28919343/characterizing-pathology-in-erythrocytes-using-morphological-and-biophysical-membrane-properties-relation-to-impaired-hemorheology-and-cardiovascular-function-in-rheumatoid-arthritis
#20
Oore-Ofe O Olumuyiwa-Akeredolu, Prashilla Soma, Antoinette V Buys, Legesse Kassa Debusho, Etheresia Pretorius
The inflammatory burden of the complex rheumatoid arthritis (RA) disease affects several organ-systems, including rheological properties of blood and its formed elements. Red blood cells (RBCs) are constantly exposed to circulating dysregulated inflammatory molecules that are co-transported within the vasculature; and their membranes may be particularly vulnerable to the accompanying oxidative stress. In the current study, we investigate biophysical and ultrastructural characteristics of RBCs obtained from a cohort of patients using atomic force microscopy (AFM), scanning electron microscopy (SEM) and confocal microscopy (CM)...
December 2017: Biochimica et Biophysica Acta
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