Effects of structure on flow mechanics in the human left ventricle and respiratory tract

2011 Summer.Includes bibliographical references.Cardiac and respiratory dysfunctions represent a large portion of healthcare problems in the United States. Many of these problems are caused by abnormal flow mechanics due to altered anatomical structure. This structure in the human body is very complex and ranges over many different scales. At relatively small scales, one facet that is still not well understood is the role of trabeculae on the biomechanics of the left ventricle. Similarly, large-scale airflow through the respiratory tract has not been fully investigated as a function of age or mechanical ventilation. This research has revealed some of the flow patterns caused by these different scale structures. Fractal geometry was used to help characterize the inner surface of the left ventricle at different times during the cardiac cycle. The fractal dimension of the ventricle was determined using a custom box-counting algorithm developed in MATLAB, and it was shown that trabeculae do indeed play a role in the biomechanics of heart pumping. Computational fluid dynamics (CFD) was also run on the respiratory tracts of three different patients to determine airflow effects due to age and intubation. Three dimensional models were constructed from computed tomography (CT) scans and simulations were run in ANSYS Fluent. Results of the study were validated through grid and time step sensitivity studies as well as comparison to previous studies. It was shown that flow mechanics in the airways of children change with age as well as with the introduction of an intubation tube

Metal-only Lewis pairs between group 10 metals and Tl(I) or Ag(I): insights into the electronic consequences of Z-type ligand binding†

Complexes bearing electron rich transition metal centers, especially those displaying coordinative unsaturation, are well-suited to form reverse-dative σ-interactions with Lewis acids. Herein we demonstrate the generality of zerovalent, group 10 m-terphenyl isocyanide complexes to form reverse-dative σ-interactions to Tl(I) and Ag(I) centers. Structural and spectroscopic investigations of these metal-only Lewis pairs (MOLPs) has allowed insight into the electronic consequences of Lewis-acid ligation within the primary coordination sphere of a transition metal center. Treatment of the bis-isocyanide complex, Pt(CNArDipp2)2 (ArDipp2 = 2,6-(2,6-(i-Pr)2C6H3)2C6H3) with TlOTf (OTf = [O3SCF3]−) yields the Pt/Tl MOLP [TlPt(CNArDipp2)2]OTf (1). 1H NMR and IR spectroscopic studies on 1, and its Pd congener [TlPd(CNArDipp2)2]OTf (2), demonstrate that the M → Tl interaction is labile in solution. However, treatment of complexes 1 and 2 with Na[BArF4] (ArF = 3,5-(CF3)2C6H3) produces [TlPt(CNArDipp2)2]BArF4 (3) and [TlPd(CNArDipp2)2]BArF4 (4), in which Tl(I) binding is shown to be static by IR spectroscopy and, in the case of 3, 195Pt NMR spectroscopy as well. This result provides strong evidence that the M → Tl linkages can be attributed primarily to σ-donation from the group 10 metal to Tl, as loss of ionic stabilization of Tl by the triflate anion is compensated for by increasing the degree of M → Tl σ-donation. In addition, X-ray Absorption Near-Edge Spectroscopy (XANES) on the Pd/Tl and Ni/Tl MOLPs, [TlPd(CNArDipp2)2]OTf (2) and [TlNi(CNArMes2)3]OTf, respectively, is used to illustrate that the formation of a reverse-dative σ-interaction with Tl(I) does not alter the spectroscopic oxidation state of the group 10 metal. Also reported is the ability of M(CNArDipp2)2 (M = Pt, Pd) to form MOLPs with Ag(I), yielding the complexes [AgM(CNArDipp2)2]OTf (5, M = Pt; 6, M = Pd). As was determined for the Tl-containing MOLPs 1–4, it is shown that the spectroscopic oxidation states of the group 10 metal in 5 and 6 are essentially unchanged compared to the zerovalent precursors M(CNArDipp2)2. However, in the case of 5 and 6, the formation of a dative M → Ag σ-bonding interaction facilitates the binding of Lewis bases to the group 10 metal trans to Ag, illustrating the potential of acceptor fragments to open up new coordination sites on transition metal complexes without formal, two-electron oxidation

Chandra Discovery of 10 New X-Ray Jets Associated With FR II Radio Core-Selected AGNs in the MOJAVE Sample

The Chandra X-ray observatory has proven to be a vital tool for studying high-energy emission processes in jets associated with Active Galactic Nuclei (AGN).We have compiled a sample of 27 AGN selected from the radio flux-limited MOJAVE (Monitoring of Jets in AGN with VLBA Experiments) sample of highly relativistically beamed jets to look for correlations between X-ray and radio emission on kiloparsec scales. The sample consists of all MOJAVE quasars which have over 100 mJy of extended radio emission at 1.4 GHz and a radio structure of at least 3" in size. Previous Chandra observations have revealed X-ray jets in 11 of 14 members of the sample, and we have carried out new observations of the remaining 13 sources. Of the latter, 10 have Xray jets, bringing the overall detection rate to ~ 78%. Our selection criteria, which is based on highly compact, relativistically beamed jet emission and large extended radio flux, thus provides an effective method of discovering new X-ray jets associated with AGN. The detected X-ray jet morphologies are generally well correlated with the radio emission, except for those displaying sharp bends in the radio band. The X-ray emission mechanism for these powerful FR II (Fanaroff-Riley type II) jets can be interpreted as inverse Compton scattering off of cosmic microwave background (IC/CMB) photons by the electrons in the relativistic jets. We derive viewing angles for the jets, assuming a non-bending, non-decelerating model, by using superluminal parsec scale speeds along with parameters derived from the inverse Compton X-ray model. We use these angles to calculate best fit Doppler and bulk Lorentz factors for the jets, as well as their possible ranges, which leads to extreme values for the bulk Lorentz factor in some cases. When both the non-bending and non-decelerating assumptions are relaxed [abridged]Comment: 38 Pages, 4 Figures, 5 Tables, accepted for publication in Ap

Identification of a Core Amino Acid Motif within the α Subunit of GABAARs that Promotes Inhibitory Synaptogenesis and Resilience to Seizures

The fidelity of inhibitory neurotransmission is dependent on the accumulation of γ-aminobutyric acid type A receptors (GABAARs) at the appropriate synaptic sites. Synaptic GABAARs are constructed from α(1-3), β(1-3), and γ2 subunits, and neurons can target these subtypes to specific synapses. Here, we identify a 15-amino acid inhibitory synapse targeting motif (ISTM) within the α2 subunit that promotes the association between GABAARs and the inhibitory scaffold proteins collybistin and gephyrin. Using mice in which the ISTM has been introduced into the α1 subunit (Gabra1-2 mice), we show that the ISTM is critical for axo-axonic synapse formation, the efficacy of GABAergic neurotransmission, and seizure sensitivity. The Gabra1-2 mutation rescues seizure-induced lethality in Gabra2-1 mice, which lack axo-axonic synapses due to the deletion of the ISTM from the α2 subunit. Taken together, our data demonstrate that the ISTM plays a critical role in promoting inhibitory synapse formation, both in the axonic and somatodendritic compartments

TCR hypervariable regions expressed by T cells that respond to effective tumor vaccines

A major goal of immunotherapy for cancer is the activation of T cell responses against tumor-associated antigens (TAAs). One important strategy for improving antitumor immunity is vaccination with peptide variants of TAAs. Understanding the mechanisms underlying the expansion of T cells that respond to the native tumor antigen is an important step in developing effective peptide-variant vaccines. Using an immunogenic mouse colon cancer model, we compare the binding properties and the TCR genes expressed by T cells elicited by peptide variants that elicit variable antitumor immunity directly ex vivo. The steady-state affinity of the natural tumor antigen for the T cells responding to effective peptide vaccines was higher relative to ineffective peptides, consistent with their improved function. Ex vivo analysis showed that T cells responding to the effective peptides expressed a CDR3β motif, which was also shared by T cells responding to the natural antigen and not those responding to the less effective peptide vaccines. Importantly, these data demonstrate that peptide vaccines can expand T cells that naturally respond to tumor antigens, resulting in more effective antitumor immunity. Future immunotherapies may require similar stringent analysis of the responding T cells to select optimal peptides as vaccine candidates. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00262-012-1217-5) contains supplementary material, which is available to authorized users

Association of Inactive Myostatin in Piedmontese-Influenced Steers and Heifers on Performance and Carcass Traits at Different Endpoints

Performance and carcass traits were evaluated using Piedmontese-influenced calf-fed steers and yearling heifers genotyped for zero, one, or two copies (homozygous active, heterozygous, or homozygous inactive, respectively) of the inactive myostatin allele. Steers and heifers had similar responses across genotypes in performance and carcass traits evaluated at different endpoints. Inactive myostatin decreased DMI, final BW (live), and ADG (live). Increased dressing percentage resulted in increased carcass-adjusted ADG and improved feed conversion for cattle with inactive myostatin. Cattle with inactive myostatin are leaner with larger LM area when finished to equal carcass weight

Phylogenomic Analyses Reveal the Evolutionary Origin of the Inhibin α-Subunit, a Unique TGFβ Superfamily Antagonist

Transforming growth factor-beta (TGFβ) homologues form a diverse superfamily that arose early in animal evolution and control cellular function through membrane-spanning, conserved serine-threonine kinases (RII and RI receptors). Activin and inhibin are related dimers within the TGFβ superfamily that share a common β-subunit. The evolution of the inhibin α-subunit created the only antagonist within the TGFβ superfamily and the only member known to act as an endocrine hormone. This hormone introduced a new level of complexity and control to vertebrate reproductive function. The novel functions of the inhibin α-subunit appear to reflect specific insertion-deletion changes within the inhibin β-subunit that occurred during evolution. Using phylogenomic analysis, we correlated specific insertions with the acquisition of distinct functions that underlie the phenotypic complexity of vertebrate reproductive processes. This phylogenomic approach presents a new way of understanding the structure-function relationships between inhibin, activin, and the larger TGFβ superfamily

Larger females have more calves: influence of maternal body length on fecundity in North Atlantic right whales

© The Author(s), 2022. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Stewart, J., Durban, J., Europe, H., Fearnbach, H., Hamilton, P., Knowlton, A., Lynn, M., Miller, C., Perryman, W., Tao, B., & Moore, M. Larger females have more calves: influence of maternal body length on fecundity in North Atlantic right whales. Marine Ecology Progress Series, 689, (2022): 179–189, https://doi.org/10.3354/meps14040.North Atlantic right whales (NARW) are critically endangered and have been declining in abundance since 2011. In the past decade, human-caused mortalities from vessel strikes and entanglements have been increasing, while birth rates in the population are at a 40 yr low. In addition to declining abundance, recent studies have shown that NARW length-at-age is decreasing due to the energetic impacts of sub-lethal entanglements, and that the body condition of the population is poorer than closely related southern right whales. We examined whether shorter body lengths are associated with reduced fecundity in female NARW. We compared age-corrected, modeled metrics of body length with 3 metrics of fecundity: age at first reproduction, average inter-birth interval, and the number of calves produced per potential reproductive year. We found that body length is significantly related to birth interval and calves produced per reproductive year, but not age at first reproduction. Larger whales had shorter inter-birth intervals and produced more calves per potential reproductive year. Larger whales also had higher lifetime calf production, but this was a result of larger whales having longer potential reproductive spans, as body lengths have generally been declining over the past 40 yr. Declining body sizes are a potential contributor to low birth rates over the past decade. Efforts to reduce entanglements and vessel strikes could help maintain population viability by increasing fecundity and improving resiliency of the population to other anthropogenic and climate impacts.Funding to the New England Aquarium for curation of the photo-identification catalog is provided by NOAA Contract 1305M2- 18-P-NFFM-0108

BpaB, a Novel Protein Encoded by the Lyme Disease Spirochete\u27s Cp32 Prophages, Binds to Erp Operator 2 DNA

Borrelia burgdorferi produces Erp outer surface proteins throughout mammalian infection, but represses their synthesis during colonization of vector ticks. A DNA region 5′ of the start of erp transcription, Operator 2, was previously shown to be essential for regulation of expression. We now report identification and characterization of a novel erp Operator 2-binding protein, which we named BpaB. erp operons are located on episomal cp32 prophages, and a single bacterium may contain as many as 10 different cp32s. Each cp32 family member encodes a unique BpaB protein, yet the three tested cp32-encoded BpaB alleles all bound to the same DNA sequence. A 20-bp region of erp Operator 2 was determined to be essential for BpaB binding, and initial protein binding to that site was required for binding of additional BpaB molecules. A 36-residue region near the BpaB carboxy terminus was found to be essential for high-affinity DNA-binding. BpaB competed for binding to erp Operator 2 with a second B. burgdorferi DNA-binding protein, EbfC. Thus, cellular levels of free BpaB and EbfC could potentially control erp transcription levels

BpaB, a novel protein encoded by the Lyme disease spirochete’s cp32 prophages, binds to erp Operator 2 DNA

Borrelia burgdorferi produces Erp outer surface proteins throughout mammalian infection, but represses their synthesis during colonization of vector ticks. A DNA region 5′ of the start of erp transcription, Operator 2, was previously shown to be essential for regulation of expression. We now report identification and characterization of a novel erp Operator 2-binding protein, which we named BpaB. erp operons are located on episomal cp32 prophages, and a single bacterium may contain as many as 10 different cp32s. Each cp32 family member encodes a unique BpaB protein, yet the three tested cp32-encoded BpaB alleles all bound to the same DNA sequence. A 20-bp region of erp Operator 2 was determined to be essential for BpaB binding, and initial protein binding to that site was required for binding of additional BpaB molecules. A 36-residue region near the BpaB carboxy terminus was found to be essential for high-affinity DNA-binding. BpaB competed for binding to erp Operator 2 with a second B. burgdorferi DNA-binding protein, EbfC. Thus, cellular levels of free BpaB and EbfC could potentially control erp transcription levels