A Mathematical Framework for Predicting Lifestyles of Viral Pathogens.

Despite being similar in structure, functioning, and size, viral pathogens enjoy very different, usually well-defined ways of life. They occupy their hosts for a few days (influenza), for a few weeks (measles), or even lifelong (HCV), which manifests in acute or chronic infections. The various transmission routes (airborne, via direct physical contact, etc.

Model-based exploration of the impact of glucose metabolism on the estrous cycle dynamics in dairy cows.

Background: Nutrition plays a crucial role in regulating reproductive hormones and follicular development in cattle. This is visible particularly during the time of negative energy balance at the onset of milk production after calving. Here, elongated periods of anovulation have been observed, resulting from alterations in luteinizing hormone concentrations, likely caused by lower glucose and insulin concentrations in the blood.

Follicular competition in cows: the selection of dominant follicles as a synergistic effect.

The reproductive cycle of mono-ovulatory species such as cows or humans is known to show two or more waves of follicular growth and decline between two successive ovulations. Within each wave, there is one dominant follicle escorted by subordinate follicles of varying number. Under the surge of the luteinizing hormone a growing dominant follicle ovulates.

Device-Embedded Cameras for Eye Tracking-Based Cognitive Assessment: Validation With Paper-Pencil and Computerized Cognitive Composites.

Background: As eye tracking-based assessment of cognition becomes more widely used in older adults, particularly those at risk for dementia, reliable and scalable methods to collect high-quality data are required. Eye tracking-based cognitive tests that utilize device-embedded cameras have the potential to reach large numbers of people as a screening tool for preclinical cognitive decline. However, to fully validate this approach, more empirical evidence about the comparability of eyetracking-based paradigms to existing cognitive batteries is needed.

Reconstruction of disease transmission rates: Applications to measles, dengue, and influenza.

Transmission rates are key in understanding the spread of infectious diseases. Using the framework of compartmental models, we introduce a simple method to reconstruct time series of transmission rates directly from incidence or disease-related mortality data. The reconstruction employs differential equations, which model the time evolution of infective stages and strains.

Different ways of looking at the force between two nanocrystals.

The potential of mean force (PMF) between two nanocrystals (NCs) represents an effective interaction potential that is essential when explaining the assembly of NCs to superstructures. For a given temperature, the PMF is obtained best from molecular dynamics simulations. Based on a density functional approach, this study proposes three methods of predicting the PMF for any given temperature based on a single molecular dynamics simulation for one temperature.

Hippo/Yap signaling controls epithelial progenitor cell proliferation and differentiation in the embryonic and adult lung.

The Hippo/Yap pathway is a well-conserved signaling cascade that regulates cell proliferation and differentiation to control organ size and stem/progenitor cell behavior. Following airway injury, Yap was dynamically regulated in regenerating airway epithelial cells. To determine the role of Hippo signaling in the lung, the mammalian Hippo kinases, Mst1 and Mst2, were deleted in epithelial cells of the embryonic and mature mouse lung.

Sox17 is required for normal pulmonary vascular morphogenesis.

The SRY-box containing transcription factor Sox17 is required for endoderm formation and vascular morphogenesis during embryonic development. In the lung, Sox17 is expressed in mesenchymal progenitors of the embryonic pulmonary vasculature and is restricted to vascular endothelial cells in the mature lung. Conditional deletion of Sox17 in splanchnic mesenchyme-derivatives using Dermo1-Cre resulted in substantial loss of Sox17 from developing pulmonary vascular endothelial cells and caused pulmonary vascular abnormalities before birth, including pulmonary vein varices, enlarged arteries, and decreased perfusion of the microvasculature.

Inkjet printed solar cell active layers based on a novel, amorphous polymer.

Organic solar cells are a favorable alternative to their inorganic counterparts because the functional layers of these devices can be processed with printing or coating on a large scale. In this study, a novel polymer was synthesized, blended with fullerene and deposited with inkjet printing for solar cell applications. Devices with printed layers were compared to those with spin coated films in order to evaluate inkjet printing as a thin film deposition method.

NFATC1 promotes epicardium-derived cell invasion into myocardium.

Epicardium-derived cells (EPDCs) contribute to formation of coronary vessels and fibrous matrix of the mature heart. Nuclear factor of activated T-cells cytoplasmic 1 (NFATC1) is expressed in cells of the proepicardium (PE), epicardium and EPDCs in mouse and chick embryos. Conditional loss of NFATC1 expression in EPDCs in mice causes embryonic death by E18.

Sox2 activates cell proliferation and differentiation in the respiratory epithelium.

Sox2, a transcription factor critical for the maintenance of embryonic stem cells and induction of pluripotent stem cells, is expressed exclusively in the conducting airway epithelium of the lung, where it is required for differentiation of nonciliated, goblet, and ciliated cells. To determine the role of Sox2 in respiratory epithelial cells, Sox2 was selectively and conditionally expressed in nonciliated airway epithelial cells and in alveolar type II cells in the adult mouse. Sox2 induced epithelial cell proliferation within 3 days of expression.

Sox2 is required for maintenance and differentiation of bronchiolar Clara, ciliated, and goblet cells.

The bronchioles of the murine lung are lined by a simple columnar epithelium composed of ciliated, Clara, and goblet cells that together mediate barrier function, mucociliary clearance and innate host defense, vital for pulmonary homeostasis. In the present work, we demonstrate that expression of Sox2 in Clara cells is required for the differentiation of ciliated, Clara, and goblet cells that line the bronchioles of the postnatal lung. The gene was selectively deleted in Clara cells utilizing Scgb1a1-Cre, causing the progressive loss of Sox2 in the bronchioles during perinatal and postnatal development.

Antigenic diversity, transmission mechanisms, and the evolution of pathogens.

Pathogens have evolved diverse strategies to maximize their transmission fitness. Here we investigate these strategies for directly transmitted pathogens using mathematical models of disease pathogenesis and transmission, modeling fitness as a function of within- and between-host pathogen dynamics. The within-host model includes realistic constraints on pathogen replication via resource depletion and cross-immunity between pathogen strains.

Sox17 promotes cell cycle progression and inhibits TGF-beta/Smad3 signaling to initiate progenitor cell behavior in the respiratory epithelium.

The Sry-related high mobility group box transcription factor Sox17 is required for diverse developmental processes including endoderm formation, vascular development, and fetal hematopoietic stem cell maintenance. Expression of Sox17 in mature respiratory epithelial cells causes proliferation and lineage respecification, suggesting that Sox17 can alter adult lung progenitor cell fate. In this paper, we identify mechanisms by which Sox17 influences lung epithelial progenitor cell behavior and reprograms cell fate in the mature respiratory epithelium.

Bayesian approximations and extensions: optimal decisions for small brains and possibly big ones too.

We compared the performance of Bayesian learning strategies and approximations to such strategies, which are far less computationally demanding, in a setting requiring individuals to make binary decisions based on experience. Extending Bayesian updating schemes, we compared the different strategies while allowing for various implementations of memory and knowledge about the environment. The dynamics of the observable variables was modeled through basic probability distributions and convolution.

Fatal gastrointestinal obstruction and hypertension in mice lacking nitric oxide-sensitive guanylyl cyclase.

The signaling molecule nitric oxide (NO), first described as endothelium-derived relaxing factor (EDRF), acts as physiological activator of NO-sensitive guanylyl cyclase (NO-GC) in the cardiovascular, gastrointestinal, and nervous systems. Besides NO-GC, other NO targets have been proposed; however, their particular contribution still remains unclear. Here, we generated mice deficient for the beta1 subunit of NO-GC, which resulted in complete loss of the enzyme.

NFATc1 expression in the developing heart valves is responsive to the RANKL pathway and is required for endocardial expression of cathepsin K.

NFATc1 is necessary for remodeling endocardial cushions into mature heart valve leaflets and is also an essential effector of receptor activator of NFkappaB ligand (RANKL) signaling required for transcriptional activation of bone matrix remodeling enzymes during osteoclast differentiation. Therefore, developing heart valves were examined to determine if NFATc1 functions in the RANKL pathway during leaflet remodeling. Key components of RANKL signal transduction including RANKL, its receptor RANK, and the downstream remodeling enzyme cathepsin K (Ctsk) are expressed in the heart during valve remodeling and colocalize with NFATc1 in developing valve endocardium.

Hearts and bones: shared regulatory mechanisms in heart valve, cartilage, tendon, and bone development.

The mature heart valves are dynamic structures composed of highly organized cell lineages and extracellular matrices. The discrete architecture of connective tissue within valve leaflets and supporting structures allows the valve to withstand life-long functional demands and changes in hemodynamic forces and load. The dysregulation of ECM organization is a common feature of heart valve disease and can often be linked to genetic defects in matrix protein structure or developmental regulation.

Desensitization of NO/cGMP signaling in smooth muscle: blood vessels versus airways.

The NO/cGMP signaling pathway plays a major role in the cardiovascular system, in which it is involved in the regulation of smooth muscle tone and inhibition of platelet aggregation. Under pathophysiological conditions such as endothelial dysfunction, coronary artery disease, and airway hyperreactivity, smooth muscle containing arteries and bronchi are of great pharmacological interest. In these tissues, NO mediates its effects by stimulating guanylyl cyclase (GC) to form cGMP; the subsequent increase in cGMP is counteracted by the cGMP-specific phosphodiesterase (PDE5), which hydrolyzes cGMP.

Impact of FDG PET for staging of Ewing sarcomas and primitive neuroectodermal tumours.

Aim: High-grade Ewing sarcomas and Primitive neuroectodermal tumours (PNET) make up the tumours of the Ewing family. Our purpose was to evaluate the value of [18F]fluorodeoxyglucose positron emission tomography (FDG PET) in patients with Ewing tumours.

Patients And Methods: Twenty-four patients who had PET because of a suspected Ewing tumour during a 5-year period were included in this retrospective study.

Restoration of DSCR1 to disomy in the trisomy 16 mouse model of Down syndrome does not correct cardiac or craniofacial development anomalies.

The Down syndrome critical region 1 (DSCR1) gene is located in syntenic regions of human chromosome 21 and mouse chromosome 16 and encodes a regulatory protein in the calcineurin/NFAT pathway. DSCR1 expression in the embryonic brain, craniofacial structures, and heart is consistent with a role in contributing to Down syndrome developmental anomalies. In the trisomy 16 (Ts16) murine model of Down syndrome, expression of DSCR1 isoforms is elevated and NFAT transcriptional activity is decreased in the developing heart and brain.

DSCR1 gene expression is dependent on NFATc1 during cardiac valve formation and colocalizes with anomalous organ development in trisomy 16 mice.

The Down syndrome critical region 1 (DSCR1) gene is present in the region of human chromosome 21 and the syntenic region of mouse chromosome 16, trisomy of which is associated with congenital heart defects observed in Down syndrome. DSCR1 encodes a regulatory protein in the calcineurin/NFAT signal transduction pathway. During valvuloseptal development in the heart, DSCR1 is expressed in the endocardium of the developing atrioventricular and semilunar valves, the muscular interventricular septum, and the ventricular myocardium.