Taxonomic status of Myotis occultus

The taxonomic status of the Arizona myotis (Myotis occultus) is uncertain. Although the taxon was described as a distinct species and currently is regarded as such by some authors, others have noted what they interpreted as intergradation with the little brown bat (M. lucifugus carissima) near the Colorado-New Mexico state line. In this study, we used protein electrophoresis to compare bats of these nominal taxa. We examined 20 loci from 142 specimens referable to M. occultus and M. lucifugus from New Mexico, Colorado, and Wyoming. Nine of the 20 loci were polymorphic. Results show that there were high similarities among samples, no fixed alleles, and minor divergence from Hardy-Weinberg equilibrium. Our results suggest that the two nominal taxa represent only one species and that M. occultus should be regarded as a subspecies of M. lucifugus

Human Vascular Tissue Models Formed from Human Induced Pluripotent Stem Cell Derived Endothelial Cells

Here we describe a strategy to model blood vessel development using a well-defined induced pluripotent stem cell-derived endothelial cell type (iPSC-EC) cultured within engineered platforms that mimic the 3D microenvironment. The iPSC-ECs used here were first characterized by expression of endothelial markers and functional properties that included VEGF responsiveness, TNF-α-induced upregulation of cell adhesion molecules (MCAM/CD146; ICAM1/CD54), thrombin-dependent barrier function, shear stress-induced alignment, and 2D and 3D capillary-like network formation in Matrigel. The iPSC-ECs also formed 3D vascular networks in a variety of engineering contexts, yielded perfusable, interconnected lumen when co-cultured with primary human fibroblasts, and aligned with flow in microfluidics devices. iPSC-EC function during tubule network formation, barrier formation, and sprouting was consistent with that of primary ECs, and the results suggest a VEGF-independent mechanism for sprouting, which is relevant to therapeutic anti-angiogenesis strategies. Our combined results demonstrate the feasibility of using a well-defined, stable source of iPSC-ECs to model blood vessel formation within a variety of contexts using standard in vitro formats.National Institutes of Health (U.S.) (NIH 1UH2 TR000506-01)National Institutes of Health (U.S.) (3UH2 TR000506-02S1)National Institutes of Health (U.S.) (T32 HL007936-12)National Institutes of Health (U.S.) (RO1 HL093282)National Institutes of Health (U.S.) (R21 EB016381-01

Hydrolytic Reactivity Trends among Potential Prodrugs of the O2-Glycosylated Diazeniumdiolate Family. Targeting Nitric Oxide to Macrophages for Antileishmanial Activity

Glycosylated diazeniumdiolates of structure R2NN(O)dNO-R ′ (R ′ ) a saccharide residue) are potential prodrugs of the nitric oxide (NO)-releasing but acid-sensitive R2NN(O)dNO- ion. Moreover, cleaving the acid-stable glycosides under alkaline conditions provides a convenient protecting group strategy for diazeniumdiolate ions. Here, we report comparative hydrolysis rate data for five representative glycosylated diazeniumdiolates at pH 14, 7.4, and 3.8-4.6 as background for further developing both the protecting group application and the ability to target NO pharmacologically to macrophages harboring intracellular pathogens. Confirming the potential in the latter application, adding R2NN(O)dNO-GlcNAc (where R2N) diethylamino or pyrrolidin-l-yl and GlcNAc) N-acetylglucosamin-l-yl) to cultures of infected mouse macrophages that were deficient in inducible NO synthase caused rapid death of the intracellular protozoan parasite Leishmania major with no host cell toxicity

Increased Matrix Metalloproteinase (MMPs) Levels Do Not Predict Disease Severity or Progression in Emphysema

Rationale: Though matrix metalloproteinases (MMPs) are critical in the pathogenesis of COPD, their utility as a disease biomarker remains uncertain. This study aimed to determine whether bronchoalveolar lavage (BALF) or plasma MMP measurements correlated with disease severity or functional decline in emphysema. Methods: Enzyme-linked immunosorbent assay and luminex assays measured MMP-1, -9, -12 and tissue inhibitor of matrix metalloproteinase-1 in the BALF and plasma of non-smokers, smokers with normal lung function and moderate-to-severe emphysema subjects. In the cohort of 101 emphysema subjects correlative analyses were done to determine if MMP or TIMP-1 levels were associated with key disease parameters or change in lung function over an 18-month time period. Main Results: Compared to non-smoking controls, MMP and TIMP-1 BALF levels were significantly elevated in the emphysema cohort. Though MMP-1 was elevated in both the normal smoker and emphysema groups, collagenase activity was only increased in the emphysema subjects. In contrast to BALF, plasma MMP-9 and TIMP-1 levels were actually decreased in the emphysema cohort compared to the control groups. Both in the BALF and plasma, MMP and TIMP-1 measurements in the emphysema subjects did not correlate with important disease parameters and were not predictive of subsequent functional decline. Conclusions: MMPs are altered in the BALF and plasma of emphysema; however, the changes in MMPs correlate poorly with parameters of disease intensity or progression. Though MMPs are pivotal in the pathogenesis of COPD, these findings suggest that measuring MMPs will have limited utility as a prognostic marker in this disease. © 2013 D'Armiento et al

Centralized Otolaryngology Research Efforts: Stepping‐stones to Innovation and Equity in Otolaryngology–Head and Neck Surgery

The Centralized Otolaryngology Research Efforts (CORE) grant program coordinates research funding initiatives across the subspecialties of otolaryngology-head and neck surgery. Modeled after National Institutes of Health study sections, CORE grant review processes provide comprehensive reviews of scientific proposals. The organizational structure and grant review process support grant-writing skills, attention to study design, and other components of academic maturation toward securing external grants from the National Institutes of Health or other agencies. As a learning community and a catalyst for scientific advances, CORE evaluates clinical, translational, basic science, and health services research. Amid the societal reckoning around long-standing social injustices and health inequities, an important question is to what extent CORE engenders diversity, equity, and inclusion for the otolaryngology workforce. This commentary explores CORE's track record as a stepping-stone for promoting equity and innovation in the specialty. Such insights can help maximize opportunities for cultivating diverse leaders across the career continuum

Brute-Force Mapmaking with Compact Interferometers: A MITEoR Northern Sky Map from 128 MHz to 175 MHz

We present a new method for interferometric imaging that is ideal for the large fields of view and compact arrays common in 21 cm cosmology. We first demonstrate the method with the simulations for two very different low-frequency interferometers, the Murchison Widefield Array and the MIT Epoch of Reionization (MITEoR) experiment. We then apply the method to the MITEoR data set collected in 2013 July to obtain the first northern sky map from 128 to 175 MHz at ∼2° resolution and find an overall spectral index of −2.73 ± 0.11. The success of this imaging method bodes well for upcoming compact redundant low-frequency arrays such as Hydrogen Epoch of Reionization Array. Both the MITEoR interferometric data and the 150 MHz sky map are available at http://space.mit.edu/home/tegmark/omniscope.html.National Science Foundation (U.S.) (AST-0908848)National Science Foundation (U.S.) (AST-1105835)National Science Foundation (U.S.) (AST-1440343

Mapping our universe in 3D with MITEoR

Mapping our universe in 3D by imaging the redshifted 21 cm line from neutral hydrogen has the potential to overtake the cosmic microwave background as our most powerful cosmological probe, because it can map a much larger volume of our Universe, shedding new light on the epoch of reionization, inflation, dark matter, dark energy, and neutrino masses. We report on MITEoR, a pathfinder low-frequency radio interferometer whose goal is to test technologies that greatly reduce the cost of such 3D mapping for a given sensitivity. MITEoR accomplishes this by using massive baseline redundancy both to enable automated precision calibration and to cut the correlator cost scaling from N[superscript 2] to N log N, where N is the number of antennas. The success of MITEoR with its 64 dual-polarization elements bodes well for the more ambitious HERA project, which incorporates many identical or similar technologies using an order of magnitude more antennas, each with dramatically larger collecting area.National Science Foundation (U.S.) (Grant AST-0908848)National Science Foundation (U.S.) (Grant AST-1105835)MIT Kavli Instrumentation FundMassachusetts Institute of Technology. Undergraduate Research Opportunities Progra

Cigarette Smoke Toxins Deposited on Surfaces: Implications for Human Health

Cigarette smoking remains a significant health threat for smokers and nonsmokers alike. Secondhand smoke (SHS) is intrinsically more toxic than directly inhaled smoke. Recently, a new threat has been discovered – Thirdhand smoke (THS) – the accumulation of SHS on surfaces that ages with time, becoming progressively more toxic. THS is a potential health threat to children, spouses of smokers and workers in environments where smoking is or has been allowed. The goal of this study is to investigate the effects of THS on liver, lung, skin healing, and behavior, using an animal model exposed to THS under conditions that mimic exposure of humans. THS-exposed mice show alterations in multiple organ systems and excrete levels of NNAL (a tobacco-specific carcinogen biomarker) similar to those found in children exposed to SHS (and consequently to THS). In liver, THS leads to increased lipid levels and non-alcoholic fatty liver disease, a precursor to cirrhosis and cancer and a potential contributor to cardiovascular disease. In lung, THS stimulates excess collagen production and high levels of inflammatory cytokines, suggesting propensity for fibrosis with implications for inflammation-induced diseases such as chronic obstructive pulmonary disease and asthma. In wounded skin, healing in THS-exposed mice has many characteristics of the poor healing of surgical incisions observed in human smokers. Lastly, behavioral tests show that THS-exposed mice become hyperactive. The latter data, combined with emerging associated behavioral problems in children exposed to SHS/THS, suggest that, with prolonged exposure, they may be at significant risk for developing more severe neurological disorders. These results provide a basis for studies on the toxic effects of THS in humans and inform potential regulatory policies to prevent involuntary exposure to THS