N nuclear spins of imidazole-N were hyperpolarized using NMR signal amplification by reversible exchange in shield enables alignment transfer to heteronuclei (SABRE-SHEATH). A N NMR signal enhancement of ∼2000-fold at 9.4 T is reported using parahydrogen gas (∼50% para-) and ∼0.
View Article and Find Full Text PDFDirect NMR hyperpolarization of naturally abundant (15)N sites in metronidazole is demonstrated using SABRE-SHEATH (Signal Amplification by Reversible Exchange in SHield Enables Alignment Transfer to Heteronuclei). In only a few tens of seconds, nuclear spin polarization P(15)N of up to ∼24% is achieved using parahydrogen with 80% para fraction corresponding to P(15)N ≈ 32% if ∼100% parahydrogen were employed (which would translate to a signal enhancement of ∼0.1-million-fold at 9.
View Article and Find Full Text PDFThe heterologous or non-specific effects (NSEs) of vaccines, at times defined as "off-target effects" suggest that they can affect the immune response to organisms other than their pathogen-specific intended purpose. These NSEs have been the subject of clinical, immunological and epidemiological studies and are increasingly recognized as an important biological process by a growing group of immunologists and epidemiologists. Much remain to be learned about the extent and underlying mechanisms for these effects.
View Article and Find Full Text PDFNMR with thermal polarization requires relatively concentrated samples, particularly for nuclei with low abundance and low gyromagnetic ratios, such as (15) N. We expand the substrate scope of SABRE, a recently introduced hyperpolarization method, to allow access to (15) N-enriched Schiff bases. These substrates show fractional (15) N polarization levels of up to 2 % while having only minimal (1) H enhancements.
View Article and Find Full Text PDFHorseshoe crabs are xiphosuran chelicerates, the sister group to arachnids. As such, they are important for understanding the most recent common ancestor of Euchelicerata and the evolution and diversification of Arthropoda. Limulus polyphemus is the most investigated of the four extant species of horseshoe crabs, and the structure and function of its visual system have long been a major focus of studies critical for understanding the evolution of visual systems in arthropods.
View Article and Find Full Text PDFBackground: A growing number of studies report an abnormal expression of Piwi-interacting RNAs (piRNAs) and the piRNA processing enzyme Piwi in many cancers. Whether this finding is an epiphenomenon of the chaotic molecular biology of the fast dividing, neoplastically transformed cells or is functionally relevant to tumorigenesisis is difficult to discern at present. To better understand the role of piRNAs in cancer development small laboratory fish models can make a valuable contribution.
View Article and Find Full Text PDFHigh-resolution genetic and physical maps are invaluable tools for building accurate genome assemblies, and interpreting results of genome-wide association studies (GWAS). Previous genetic and physical maps anchored good quality draft assemblies of the domestic cat genome, enabling the discovery of numerous genes underlying hereditary disease and phenotypes of interest to the biomedical science and breeding communities. However, these maps lacked sufficient marker density to order thousands of shorter scaffolds in earlier assemblies, which instead relied heavily on comparative mapping with related species.
View Article and Find Full Text PDFThe tsetse fly Glossina fuscipes fuscipes (Gff) is the insect vector of the two forms of Human African Trypanosomiasis (HAT) that exist in Uganda. Understanding Gff population dynamics, and the underlying genetics of epidemiologically relevant phenotypes is key to reducing disease transmission. Using ddRAD sequence technology, complemented with whole-genome sequencing, we developed a panel of ∼73,000 single-nucleotide polymorphisms (SNPs) distributed across the Gff genome that can be used for population genomics and to perform genome-wide-association studies.
View Article and Find Full Text PDFObjective: There are little clinical data assessing the antineoplastic effect of metformin in patients with non-small cell lung cancer. We hypothesized that in diabetic patients undergoing pulmonary resection for early-stage non-small cell lung cancer, metformin exposure is associated with improved survival.
Methods: An institutional database was used to identify patients with stage I or II non-small cell lung cancer who underwent pulmonary resection between 2004 and 2013.
Purpose: Pulmonary lobectomy with en bloc chest wall resection is a common strategy for treating lung cancers invading the chest wall. We hypothesized a direct relationship exists between number of ribs resected and postoperative respiratory complications.
Methods: An institutional database was queried for patients with non-small cell lung cancer that underwent lobectomy with en bloc chest wall resection between 2003 and 2014.
Conventional magnetic resonance (MR) faces serious sensitivity limitations which can be overcome by hyperpolarization methods, but the most common method (dynamic nuclear polarization) is complex and expensive, and applications are limited by short spin lifetimes (typically seconds) of biologically relevant molecules. We use a recently developed method, SABRE-SHEATH, to directly hyperpolarize (15)N2 magnetization and long-lived (15)N2 singlet spin order, with signal decay time constants of 5.8 and 23 minutes, respectively.
View Article and Find Full Text PDFMultiphoton microscopy has rapidly gained popularity in biomedical imaging and materials science because of its ability to provide three-dimensional images at high spatial and temporal resolution even in optically scattering environments. Currently the majority of commercial and home-built devices are based on two-photon fluorescence and harmonic generation contrast. These two contrast mechanisms are relatively easy to measure but can access only a limited range of endogenous targets.
View Article and Find Full Text PDFBackground: Hormonal action has been implicated as a possible mechanism for pregnancy-induced analgesia. Previous investigators have reported an increase in heat pain tolerance during labor compared with nonpregnant controls and postulated it was because of the hormonal changes during pregnancy. However, these previous reports did not include measurement of hormonal values.
View Article and Find Full Text PDFNeutralizing antibodies induced by vaccination or natural infection play a critically important role in protection against the viral diseases. In general, neutralization of the viral infection occurs via two major pathways: pre- and post-attachment modes, the first being the most important for such infections as influenza and polio, the latter being significant for filoviruses. Neutralizing capacity of antibodies is typically evaluated by virus neutralization assays that assess reduction of viral infectivity to the target cells in the presence of functional antibodies.
View Article and Find Full Text PDFStimulated Raman scattering (SRS) enables fast, high resolution imaging of chemical constituents important to biological structures and functional processes, both in a label-free manner and using exogenous biomarkers. While this technology has shown remarkable potential, it is currently limited to point scanning and can only probe a few Raman bands at a time (most often, only one). In this work we take a fundamentally different approach to detecting the small nonlinear signals based on dispersion effects that accompany the loss/gain processes in SRS.
View Article and Find Full Text PDFFor over 50 years, the great tit (Parus major) has been a model species for research in evolutionary, ecological and behavioural research; in particular, learning and cognition have been intensively studied. Here, to provide further insight into the molecular mechanisms behind these important traits, we de novo assemble a great tit reference genome and whole-genome re-sequence another 29 individuals from across Europe. We show an overrepresentation of genes related to neuronal functions, learning and cognition in regions under positive selection, as well as increased CpG methylation in these regions.
View Article and Find Full Text PDFIn this paper we demonstrate long-lived states involving a pair of chemically equivalent protons, with lifetimes ∼30 times T1 up to a total lifetime of ∼117s at high field (8.45T). This is demonstrated on trans-ethylene-d2 in solution, where magnetic inequivalence gives access to the long-lived states.
View Article and Find Full Text PDFBackground: Xiphophorus fishes are represented by 26 live-bearing species of tropical fish that express many attributes (e.g., viviparity, genetic and phenotypic variation, ecological adaptation, varied sexual developmental mechanisms, ability to produce fertile interspecies hybrids) that have made attractive research models for over 85 years.
View Article and Find Full Text PDFBackground. Recent trials of recombinant, live-attenuated chimeric yellow fever-dengue tetravalent dengue vaccine (CYD-TDV) demonstrated efficacy against symptomatic, virologically confirmed dengue disease with higher point estimates of efficacy toward dengue virus (DENV)3 and DENV4 and moderate levels toward DENV1 and DENV2. It is interesting to note that serotype-specific efficacy did not correlate with absolute neutralizing antibody (nAb) geometric mean titer (GMT) values measured in a Vero-based plaque reduction neutralization test assay.
View Article and Find Full Text PDFThe incidence of malignant melanoma continues to increase each year with poor prognosis for survival in many relapse cases. To reverse this trend, whole body response measures are needed to discover collaborative paths to primary and secondary malignancy. Several species of fish provide excellent melanoma models because fish and human melanocytes both appear in the epidermis, and fish and human pigment cell tumors share conserved gene expression signatures.
View Article and Find Full Text PDFRhodnius prolixus not only has served as a model organism for the study of insect physiology, but also is a major vector of Chagas disease, an illness that affects approximately seven million people worldwide. We sequenced the genome of R. prolixus, generated assembled sequences covering 95% of the genome (∼ 702 Mb), including 15,456 putative protein-coding genes, and completed comprehensive genomic analyses of this obligate blood-feeding insect.
View Article and Find Full Text PDFPhysarum polycephalum is a well-studied microbial eukaryote with unique experimental attributes relative to other experimental model organisms. It has a sophisticated life cycle with several distinct stages including amoebal, flagellated, and plasmodial cells. It is unusual in switching between open and closed mitosis according to specific life-cycle stages.
View Article and Find Full Text PDFBackground: The Tasmanian devil (Sarcophilus harrisii) is being threatened with extinction in the wild by a disease known as devil facial tumour disease (DFTD). In order to prevent the spread of this disease a thorough understanding of the Tasmanian devil immune system and its response to the disease is required. In 2011 and 2012 two genome sequencing projects of the Tasmania devil were released.
View Article and Find Full Text PDF