Non-healing bone defects are a pressing public health concern accounting for one main cause for decreased life expectancy and quality. An aging population accompanied with increasing incidence of comorbidities, foreshadows a worsening of this socio-economic problem. Conventional treatments for non-healing bone defects prove ineffective for 5%-10% of fractures.
View Article and Find Full Text PDFDefective interfering particles (DIPs) are regarded as potent broad-spectrum antivirals. We developed a mathematical model that describes intracellular co-infection dynamics of influenza standard virus (STV) and "OP7", a new type of influenza DIP discovered recently. Based on experimental data from studies to calibrate the model and confirm its predictions, we deduce OP7's mechanisms of interference, which were yet unknown.
View Article and Find Full Text PDFProteomics technologies, which include a diverse range of approaches such as mass spectrometry-based, array-based, and others, are key technologies for the identification of biomarkers and disease mechanisms, referred to as mechanotyping. Despite over 15,000 published studies in 2022 alone, leveraging publicly available proteomics data for biomarker identification, mechanotyping and drug target identification is not readily possible. Proteomic data addressing similar biological/biomedical questions are made available by multiple research groups in different locations using different model organisms.
View Article and Find Full Text PDFBackground: Despite centuries of research, debate remains on the scaling of metabolic rate to mass especially for intraspecific cases. The high variation of body mass within brown bears presents a unique opportunity to study the intraspecific effects of body mass on physiological variables. The amplitude of metabolic rate reduction in hibernators is dependent on body mass of the species.
View Article and Find Full Text PDFHeart rate biologging has been successfully used to study wildlife responses to natural and human-caused stressors (e.g., hunting, landscape of fear).
View Article and Find Full Text PDFSingle-cell RNA sequencing (scRNA-seq) technology provides an unprecedented opportunity to understand gene functions and interactions at single-cell resolution. While computational tools for scRNA-seq data analysis to decipher differential gene expression profiles and differential pathway expression exist, we still lack methods to learn differential regulatory disease mechanisms directly from the single-cell data. Here, we provide a new methodology, named DiNiro, to unravel such mechanisms and report them as small, easily interpretable transcriptional regulatory network modules.
View Article and Find Full Text PDFBackground: Passive integrated transponder devices (PIT tags) are a valuable tool for individual identification of animals. Similarly, the surgical implantation of transmitters and bio-loggers can provide useful data on animal location, physiology and behavior. However, to avoid unnecessary recapture and related stress of study animals, PIT tags and bio-loggers should function reliably for long periods of time.
View Article and Find Full Text PDFBiological rhythms, such as rhythms in activity and body temperature, are usually highly synchronized and entrained by environmental conditions, such as photoperiod. However, how the expression of these rhythms changes during hibernation, when the perception of environmental cues is limited, has not yet been fully understood for all hibernators, especially in the wild. The brown bear () in Scandinavia lives in a highly seasonal environment and adapts to harsh winter conditions by exhibiting hibernation, characterized by reduced metabolism and activity.
View Article and Find Full Text PDFAnthropogenic change is a major threat to individual species and biodiversity. Yet the behavioral and physiological responses of animals to these changes remain understudied. This is due to the technological challenges in assessing these effects .
View Article and Find Full Text PDFPhilos Trans R Soc Lond B Biol Sci
August 2021
The latest technologies associated with implantable physiological monitoring devices can record multiple channels of data (including: heart rates and rhythms, activity, temperature, impedance and posture), and coupled with powerful software applications, have provided novel insights into the physiology of animals in the wild. This perspective details past challenges and lessons learned from the uses and developments of implanted biologgers designed for human clinical application in our research on free-ranging American black bears (). In addition, we reference other research by colleagues and collaborators who have leveraged these devices in their work, including: brown bears (), grey wolves (), moose (), maned wolves () and southern elephant seals ().
View Article and Find Full Text PDFPhenotypic variation in cultured mammalian cell lines is known to be induced by passaging and culture conditions. Yet, the effect these variations have on the production of viral vectors has been overlooked. In this work we evaluated the impact of using Madin-Darby canine kidney (MDCK) parental cells from American Type Culture Collection (ATCC) or European Collection of Authenticated Cell Cultures (ECACC) cell bank repositories in both adherent and suspension cultures for the production of canine adenoviral vectors type 2 (CAV-2).
View Article and Find Full Text PDFA large group of biopharmaceuticals is produced in cell lines. The yield of such products can be increased by genetic engineering of the corresponding cell lines. The prediction of promising genetic modifications by mathematical modeling is a valuable tool to facilitate experimental screening.
View Article and Find Full Text PDFDefective interfering particles (DIPs) are a natural byproduct of influenza A virus (IAV) replication. DIPs interfere with the propagation and spread of infectious standard virus (STV), reduce virus yields by competing for viral and cellular resources, and induce antiviral responses. These properties open exciting possibilities for the development of DIP-based antivirals.
View Article and Find Full Text PDFPhys Rev Lett
September 2019
Cold samples of calcium atoms are prepared in the metastable ^{3}P_{1} state inside an optical cavity resonant with the narrow band (375 Hz) ^{1}S_{0}→^{3}P_{1} intercombination line at 657 nm. We observe a superradiant emission of hyperbolic secant shaped pulses into the cavity with an intensity proportional to the square of the atom number, a duration much shorter than the natural lifetime of the ^{3}P_{1} state, and a delay time fluctuating from shot to shot in excellent agreement with theoretical predictions. Our incoherent pumping scheme to produce inversion on the ^{1}S_{0}→^{3}P_{1} transition should be extendable to allow for continuous wave laser operation.
View Article and Find Full Text PDFJ Cardiovasc Electrophysiol
October 2019
Background: A direct indicator of effective pulmonary vein isolation (PVI) based on early ice formation is presently lacking.
Objective: The initial impedance rise within 30 to 60 seconds (sec) of single cryoablation relating to ice on the distal surface of the cryoballoon could; predict effective PVI with early termination, the need for prolonging the cryoablation, or failure to achieve effective ablation.
Methods: Impedance measurements were taken between two ring electrodes, at the anterior balloon surface and at the shaft behind the balloon.
The best measure to limit spread of contagious diseases caused by influenza A viruses (IAVs) is annual vaccination. The growing global demand for low-cost vaccines requires the establishment of high-yield production processes. One possible option to address this challenge is the engineering of novel vaccine producer cell lines by manipulating gene expression of host cell factors relevant for virus replication.
View Article and Find Full Text PDFInfluenza A viruses (IAV) are commonly used to infect animal cell cultures for research purposes and vaccine production. Their replication is influenced strongly by the multiplicity of infection (MOI), which ranges over several orders of magnitude depending on the respective application. So far, mathematical models of IAV replication have paid little attention to the impact of the MOI on infection dynamics and virus yields.
View Article and Find Full Text PDFUnmanned aircraft systems (UAS; i.e. 'drones') provide new opportunities for data collection in ecology, wildlife biology and conservation.
View Article and Find Full Text PDFBackground: The success of cryoablation of the pulmonary vein isolation (PVI) is dependent on transmural and circumferential ice formation. We hypothesize that rising impedance recorded from a ring electrode placed 2 mm from the cryoballoon signifies ice formation covering the balloon surface and indicates ice expansion. The impedance level enables titration of the cryoapplication time to avoid extracardiac damage while ensuring PVI.
View Article and Find Full Text PDFBackground: Pulmonary vein (PV) occlusion is essential for PV isolation (PVI) using the cryoballoon. Currently occlusion is arbitrarily determined using fluoroscopy and contrast media. This study aimed to create an objective measure without utilizing excessive fluoroscopy and using no contrast media.
View Article and Find Full Text PDFPhysiological monitoring of free-ranging wild animals is providing new insights into their adaptations to a changing environment. American black bears (Ursus americanus) are highly adaptable mammals, spending up to half the year hibernating, and the remainder of the year attempting to gain weight on a landscape with foods that vary seasonally and year to year. We recorded heart rate (HR) and corresponding activity of an adult female black bear over the course of six years, using an implanted monitor.
View Article and Find Full Text PDFHuman disturbance can affect animal life history and even population dynamics. However, the consequences of these disturbances are difficult to measure. This is especially true for hibernating animals, which are highly vulnerable to disturbance, because hibernation is a process of major physiological changes, involving conservation of energy during a resource-depleted time of year.
View Article and Find Full Text PDFRemarkably, American black bears (Ursus americanus) are capable of varying their heart rates to coincide with their breathing, creating pauses of 30 s or more, yet they do not appear to suffer from embolic events. We evaluated some features of the clotting cascade of black bears, providing novel insights into the underlying mechanisms they evoke for embolic protection during hibernation. We measured activated clotting time, prothrombin time and activated partial thromboplastin time during early denning (December), late denning (March) and summer (August).
View Article and Find Full Text PDFLike many other viral pathogens, influenza A viruses can form defective interfering particles (DIPs). These particles carry a large internal deletion in at least one of their genome segments. Thus, their replication depends on the co-infection of cells by standard viruses (STVs), which supply the viral protein(s) encoded by the defective segment.
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