The Solution Structures of Two Human IgG1 Antibodies Show Conformational Stability and Accommodate Their C1q and FcγR Ligands.

The human IgG1 antibody subclass shows distinct properties compared with the IgG2, IgG3, and IgG4 subclasses and is the most exploited subclass in therapeutic antibodies. It is the most abundant subclass, has a half-life as long as that of IgG2 and IgG4, binds the FcγR receptor, and activates complement. There is limited structural information on full-length human IgG1 because of the challenges of crystallization. To rectify this, we have studied the solution structures of two human IgG1 6a and 19a monoclonal antibodies in different buffers at different temperatures. Analytical ultracentrifugation showed that both antibodies were predominantly monomeric, with sedimentation coefficients s20,w (0) of 6.3-6.4 S. Only a minor dimer peak was observed, and the amount was not dependent on buffer conditions. Solution scattering showed that the x-ray radius of gyration Rg increased with salt concentration, whereas the neutron Rg values remained unchanged with temperature. The x-ray and neutron distance distribution curves P(r) revealed two peaks, M1 and M2, whose positions were unchanged in different buffers to indicate conformational stability. Constrained atomistic scattering modeling revealed predominantly asymmetric solution structures for both antibodies with extended hinge structures. Both structures were similar to the only known crystal structure of full-length human IgG1. The Fab conformations in both structures were suitably positioned to permit the Fc region to bind readily to its FcγR and C1q ligands without steric clashes, unlike human IgG4. Our molecular models for human IgG1 explain its immune activities, and we discuss its stability and function for therapeutic applications

Vortex Solutions in Two-Higgs-Doublet Systems

We analyze the existence of string-like defects in a two-Higgs-doublet system having $SU(2) \times U(1)_Y \times U(1)_{Y^{\prime}}$ as gauge group. We are able to show that, when certain relations among the parameters hold, these configurations satisfy a set of first order differential equations (Bogomol'nyi equations) and their energy is proportional to their topological charge.}Comment: 9 page

A Braneworld Universe From Colliding Bubbles

Much work has been devoted to the phenomenology and cosmology of the so-called braneworld universe, where our (3+1)-dimensional universe lies on a brane surrounded by a (4+1)-dimensional bulk spacetime that is essentially empty except for a negative cosmological constant and the various modes associated with gravity. For such a braneworld cosmology, the difficulty of justifying some preferred initial conditions inevitably arises. The various proposals for inflation restricted to the brane only partially explain the homogeneity and isotropy of the resulting braneworld universe because the homogeneity and isotropy of the bulk must be assumed. We propose a mechanism by which a brane surrounded by AdS space arises naturally so that the homogeneity and isotropy of both the brane and the bulk are guaranteed. We postulate an initial false vacuum phase of (4+1)-dimensional Minkowski or de Sitter space subsequently decaying to a true vacuum of anti-de Sitter space, assumed discretely degenerate. This decay takes place through bubble nucleation. When two bubbles of the true AdS vacuum collide, a brane (or domain wall) inevitably forms between the two AdS phases. We live on this brane. The SO(3,1) symmetry of the collision geometry ensures the three-dimensional spatial homogeneity and isotropy of the universe on the brane as well as of the bulk. In the semi-classical limit, this symmetry is exact. We sketch how the leading quantum corrections translate into cosmological perturbations.Comment: 15 pages Latex (seven ps figures). Minor revisions, references added and figures improve

Prescribed Fire Use Among Black Landowners in the Red Hills Region, USA

The Red Hills Region of southern Alabama, northern Florida, and southwestern Georgia is one of the most prominent areas in the United States for conducting prescribed fire research and is the birthplace of fire ecology. The culture of prescribed burning in the Red Hills has been influenced by multiple ethnic groups, including the Seminole and Creek nations, Black landowners, and White researchers. Given the distinctive reliance of the region on prescribed fire, it is noteworthy that the combined issues of Black land loss, underrepresentation, and incentives for using prescribed fire on private lands in the southeastern United States have generated questions about diversity and inclusion in landowner outreach. To increase understanding about Black landowner historic and current use of prescribed fire for land management in the Red Hills Region, formal and informal interviews were conducted from May through August 2019 with 21 Black landowners and tenants to document the perspectives and thoughts of Black landowners and tenants of southern Alabama, northern Florida, and southwestern Georgia. The results of this research show that Black landowners, tenants, and fire experts, have been, and continue to be, influential in the development and sustainment of fire traditions in the RedHills and in the resilience of the longleaf pine ecosystem

Neoclassical tearing modes in DIII-D and calculations of the stabilizing effects of localized electron cyclotron current drive

Neoclassical tearing modes are found to limit the achievable beta in many high performance discharges in DIII-D. Electron cyclotron current drive within the magnetic islands formed as the tearing mode grows has been proposed as a means of stabilizing these modes or reducing their amplitude, thereby increasing the beta limit by a factor around 1.5. Some experimental success has been obtained previously on Asdex-U. Here the authors examine the parameter range in DIII-C in which this effect can best be studied

Muscle loss following a single high-dose intramuscular injection of corticosteroids to treat disease flare in patients with rheumatoid arthritis.

OBJECTIVE: Adverse changes in body composition, specifically decreased muscle mass (MM) and increased fat mass, characterize rheumatoid arthritis (RA). These changes, termed rheumatoid cachexia (RC), are important contributors to the disability and elevated co-morbidity risk of RA. Recently, we observed substantial muscle loss (~2 kg) in a patient with RA following a single intramuscular (IM) corticosteroid (CS) injection to treat a disease flare. The aim of the current study is to determine whether this apparent iatrogenic effect of IM CS is typical, i.e., does this routine, recommended treatment contribute to RC? METHODS: Body composition was assessed by dual-energy X-ray absorptiometry (DXA) in eight patients with established RA who received a 120 mg IM methylprednisolone injection to treat a disease flare. DXA scans estimated appendicular lean mass (ALM; a surrogate measure of MM), total lean mass (LM), and total and regional adiposity at baseline (injection day) and 4 weeks and 6-9 months post-injection. Statistical analysis was performed using one-way ANOVA. RESULTS: There was significant loss of ALM (-0.93 kg, p=0.001, 95% CI [-0.49, -1.36]) and a trend toward reduced LM (-1.10 kg, p=0.165, 95% CI [0.58, -2.79]) at 4 weeks relative to baseline. At 6-9 months despite control of inflammation and disease activity, these losses remained. CONCLUSION: Substantial muscle loss occurred in patients with RA following IM CS injection to treat a disease flare. Thus, this recommended treatment appears to exacerbate RC, thereby potentially increasing disability and co-morbidity risk. If this effect is confirmed by larger studies, the role of one-off high-dose CS in the treatment of RA should be reviewed

Which factors predict candidate outcome in advanced life support courses? A preliminary observational study

PURPOSE: To identify factors associated with candidate outcome in the European Resuscitation Council (ERC) advanced life support (ALS) provider courses. METHODS: Medical doctors participating as candidates to consecutive ALS courses organised by an ERC training centre in Italy were enrolled in this prospective cohort study. The association between the ALS course outcome and candidate demographics, professional background and pre-course knowledge measured by using the pre-course multiple choice quiz (MCQ) was investigated by using logistic regression. RESULTS: A total of 283 candidates, median age 31 years, were evaluated. Among them, 269 (95.1%) passed the final evaluation and 14 (4.9%) failed. Candidates who passed were younger (median age 31 vs. 37.5 years; p = 0.006) and attained a higher pre-course MCQ score (median 84 vs. 72.5%; p < 0.0001). On multivariate analysis, a higher pre-course MCQ score (OR 1.18 [95%CI 1.09-1.28]) and a basic life support (BLS) certification (OR 5.00 [95%CI 1.12-22.42]) were independent predictors of candidate success, while older age was associated with a significantly higher risk of failing (OR 0.90 [95%CI 0.83-0.97]). Female candidates had higher pass rates (97.2 vs. 91.2%; p = 0.048); however, after correction for confounders gender was not significantly associated with candidate outcome. Neither candidate specialty nor site of work was a predictor of candidate success. CONCLUSIONS: On ALS courses, younger age and a higher level of specific pre-course knowledge, as measured by both the pre-course MCQ and the presence of BLS certification, are the most important predictors of success. Candidate gender and professional background did not show a significant correlation with course outcom

Probing the local structure: macromolecular combs in external fields

Recent experimental methods allow to monitor the response of macromolecules to locally applied fields, complementing usual, mesoscopic techniques. Based on the Rouse-model and its extension to generalized Gaussian structures (GGS), we follow here the stretching of comb macromolecules under local fields. This leads to a wealth of informations about the structure: Namely, given the inhomogeneous architecture of combs, the dynamics and amount of stretching depend strongly on the position of the monomer on which the external fields act. We discuss both the theoretical and the experimental implications of our findings, given that micromanipulations can be supplemented by fluorescence measurements, which are very sensitive to changes in the intramolecular distances.Comment: 16 pages, 5 pdf figures, to appear in Chem. Phy

Central and peripheral clocks in Atlantic bluefin tuna (Thunnus thynnus, L.): Daily rhythmicity of hepatic lipid metabolism and digestive genes

Atlantic bluefin tuna (ABT; Thunnus thynnus) is a highly regarded and consumed species, but farming is still in its infancy. Currently, nothing is known about the presence of circadian rhythmicity at central or peripheral tissues, or if there are daily rhythms in expression of genes involved in lipid metabolism. In order to elucidate clock gene regulation of genes of lipid metabolism in ABT, six clock genes (bmal1, clock, cry1, cry2, per1 and per2) were sequenced and 24 h expression of these genes determined in brain and liver of fish acclimated to a light:dark (L:D) photoperiod. Additionally, the daily expression of lipid metabolism and digestive enzyme genes in ABT was also determined in liver. All six clock genes displayed rhythmicity in the brain and liver, other than cry2, which did not show an acrophase in liver. In liver, all the transcription factors analysed other than srebp1 and srebp2 displayed rhythmicity, with lxr and pparα displaying diurnal expression, whereas pparγ was highly expressed at the end of the scotophase. Some of the target genes of lxr such as elovl5 and lpl also oscillated rhythmically, with acrophases during the photophase. In contrast, only three of the eight digestive enzyme genes studied displayed rhythmicity, at different times of the day, suggesting that either ABT display different feeding periods or the digestion of some nutrients (e.g. lipids) is prioritized over others. The present study showed that clock and lipid metabolism genes displayed strong daily rhythmicity in ABT brain and liver, which could be an area of considerable interest for the establishment of efficient feeding protocols in this new aquaculture species.En prensa2,04

Priorities for Pig Research in Southeast Asia and the Pacific to 2010

Livestock Production/Industries, Research and Development/Tech Change/Emerging Technologies,