Three-Dimensional Imaging of the Mouse Neurovasculature with Magnetic Resonance Microscopy

Knowledge of the three-dimensional (3D) architecture of blood vessels in the brain is crucial because the progression of various neuropathologies ranging from Alzheimer's disease to brain tumors involves anomalous blood vessels. The challenges in obtaining such data from patients, in conjunction with development of mouse models of neuropathology, have made the murine brain indispensable for investigating disease induced neurovascular changes. Here we describe a novel method for “whole brain” 3D mapping of murine neurovasculature using magnetic resonance microscopy (μMRI). This approach preserves the vascular and white matter tract architecture, and can be combined with complementary MRI contrast mechanisms such as diffusion tensor imaging (DTI) to examine the interplay between the vasculature and white matter reorganization that often characterizes neuropathologies. Following validation with micro computed tomography (μCT) and optical microscopy, we demonstrate the utility of this method by: (i) combined 3D imaging of angiogenesis and white matter reorganization in both, invasive and non-invasive brain tumor models; (ii) characterizing the morphological heterogeneity of the vascular phenotype in the murine brain; and (iii) conducting “multi-scale” imaging of brain tumor angiogenesis, wherein we directly compared in vivo MRI blood volume measurements with ex vivo vasculature data

A Biological Global Positioning System: Considerations for Tracking Stem Cell Behaviors in the Whole Body

Many recent research studies have proposed stem cell therapy as a treatment for cancer, spinal cord injuries, brain damage, cardiovascular disease, and other conditions. Some of these experimental therapies have been tested in small animals and, in rare cases, in humans. Medical researchers anticipate extensive clinical applications of stem cell therapy in the future. The lack of basic knowledge concerning basic stem cell biology-survival, migration, differentiation, integration in a real time manner when transplanted into damaged CNS remains an absolute bottleneck for attempt to design stem cell therapies for CNS diseases. A major challenge to the development of clinical applied stem cell therapy in medical practice remains the lack of efficient stem cell tracking methods. As a result, the fate of the vast majority of stem cells transplanted in the human central nervous system (CNS), particularly in the detrimental effects, remains unknown. The paucity of knowledge concerning basic stem cell biology—survival, migration, differentiation, integration in real-time when transplanted into damaged CNS remains a bottleneck in the attempt to design stem cell therapies for CNS diseases. Even though excellent histological techniques remain as the gold standard, no good in vivo techniques are currently available to assess the transplanted graft for migration, differentiation, or survival. To address these issues, herein we propose strategies to investigate the lineage fate determination of derived human embryonic stem cells (hESC) transplanted in vivo into the CNS. Here, we describe a comprehensive biological Global Positioning System (bGPS) to track transplanted stem cells. But, first, we review, four currently used standard methods for tracking stem cells in vivo: magnetic resonance imaging (MRI), bioluminescence imaging (BLI), positron emission tomography (PET) imaging and fluorescence imaging (FLI) with quantum dots. We summarize these modalities and propose criteria that can be employed to rank the practical usefulness for specific applications. Based on the results of this review, we argue that additional qualities are still needed to advance these modalities toward clinical applications. We then discuss an ideal procedure for labeling and tracking stem cells in vivo, finally, we present a novel imaging system based on our experiments

Recent invasion by a non-native cyprinid (common bream Abramis brama) is followed by major changes in the ecological quality of a shallow lake in southern Europe

We present an example of how an invasion by a non-native cyprinid (common bream, Abramis brama (Pisces: Cyprinidae), hereafter bream) in a natural shallow lake in southern Europe (Lake Montorfano, northern Italy) may have adversely affected the state of the lake’s ecosystem. In less than two decades, bream became the most abundant species and characterized by a stunted population with asymptotic length 33.5 cm, an estimated mean length at first maturity of 19.6 cm, a total mortality rate of 0.64 year−1 and a diet overwhelmingly dominated by microcrustaceans. Following bream establishment, nutrients and phytoplankton biomass rose, the proportion of Cyanobacteria by numbers increased markedly and water transparency decreased. Total zooplankton abundance increased with a marked increase in small cladocerans and copepods, whereas the abundance of large herbivorous cladocerans did not change. The coverage of submerged macrophytes declined, as did the abundance of native pelagic zooplanktivorous fish. The composition of the fish community shifted towards a higher proportion of zoobenthivorous species, such as bream and pumpkinseed (Lepomis gibbosus). Our results indicate that bream affected water quality through bottom-up mechanisms, while top-down effects were comparatively weak. Selective removal of bream and perhaps stocking of native piscivores might improve the ecological status of the lake

Nutritional Capability of and Substrate Suitability for Pseudogymnoascus destructans, the Causal Agent of Bat White-Nose Syndrome

Pseudogymnoascus destructans, the causal agent of bat white-nose syndrome, has caused nearly six million deaths in North American bats since its introduction into the United States in 2006. Current research has shown that caves can harbor P. destructans even after the infected bats are removed and bats no longer visit or inhabit previously infected caves. Our research focuses on elucidating reservoir requirements by investigating the nutritional capabilities of and substrate suitability requirements for six different P. destructans isolates from various localities including Illinois, Indiana, New York (Type specimen), and Pennsylvania. Enzyme assays implicate that both urease and b-glucosidase appear to be constitutive, lipase and esterase activity were more rapid than proteinase activity on 6% gelatin, gelatin degradation was accompanied by medium alkalinization, the reduction of thiosulfate generated hydrogen sulfide gas, chitinase and manganese dependent peroxidase activity were not visually demonstrated within eight weeks, and keratinase activity was not evident at pH 8 within eight weeks. We demonstrate that all P. destructans isolates are capable of growth and sporulation on dead fish, insect, and mushroom tissues. Sole nitrogen source assays demonstrated that all P. destructans isolates exhibit Class 2 nitrogen utilization and that growth-dependent interactions occur among different pH and nitrogen sources. Substrate suitability assays demonstrated that all isolates could grow and sporulate on media ranging from pH 5–11 and tolerated media supplemented with 2000 mg/L of calcium and 700 mg/L of three separated sulfur compounds: thiosulfate L-cysteine, and sulfite. All isolates were intolerant to PEG-induced matric potential with delayed germination and growth at −2.5 MPa with no visible germination at −5 MPa. Interestingly, decreasing the surface tension with Tween 80 permitted germination and growth of P. destructans in −5 MPa PEG medium within 14 days suggesting a link between substrate suitability and a