Flow measurements near a Reynolds ridge

The Reynolds ridge is a well-known phenomenon first observed in 1854 by Henry David Thoreau. It was then rediscovered by Langton in 1872, but Reynolds was the first to recognize that the surface tension difference was the physical mechanism behind its formation and saw the equality between the case of a spreading film and that of a stagnant film met by oncoming flow. However, it wasn't until McCutchen in 1970 that the prediction of a boundary layer forming beneath the film was introduced as the cause of the surface deformation rise ahead of the film due to the retardation of the flow. The first quantitative theory of the ridge was formed by Harper and Dixon (1974), who stated that the surface tension gradient balances the viscous shear stress generated in the boundary layer. Experimental studies of the ridge so far include Schlieren visualizations by Sellin (1968) as well as by Scott (1982) who measured the surface slope across the ridge and found good comparisons between the theoretical results of Harper and Dixon. Finally, it was Scott who recognized that even at very low levels of surface contamination the Reynolds ridge is found to exist

The Four types of Tregs in malignant lymphomas

Regulatory T cells (Tregs) are a specialized subpopulation of CD4+ T cells, which act to suppress the activation of other immune cells. Tregs represent important modulators for the interaction between lymphomas and host microenvironment. Lymphomas are a group of serious and frequently fatal malignant diseases of lymphocytes. Recent studies revealed that some lymphoma T cells might adopt a Treg profile. Assessment of Treg phenotypes and genotypes in patients may offer prediction of outcome in many types of lymphomas including diffuse large B-cell lymphoma, follicular lymphoma, cutaneous T cell lymphoma, and Hodgkin's lymphoma. Based on characterized roles of Tregs in lymphomas, we can categorize the various roles into four groups: (a) suppressor Tregs; (b) malignant Tregs; (c) direct tumor-killing Tregs; and (d) incompetent Tregs. The classification into four groups is significant in predicting prognosis and designing Tregs-based immunotherapies for treating lymphomas. In patients with lymphomas where Tregs serve either as suppressor Tregs or malignant Tregs, anti-tumor cytotoxicity is suppressed thus decreased numbers of Tregs are associated with a good prognosis. In contrast, in patients with lymphomas where Tregs serve as tumor-killing Tregs and incompetent Tregs, anti-tumor cytotoxicity is enhanced or anti-autoimmune Tregs activities are weakened thus increased numbers of Tregs are associated with a good prognosis and reduced numbers of Tregs are associated with a poor prognosis. However, the mechanisms underlying the various roles of Tregs in patients with lymphomas remain unknown. Therefore, further research is needed in this regard as well as the utility of Tregs as prognostic factors and therapy strategies in different lymphomas

Memory B Cell Antibodies to HIV-1 gp140 Cloned from Individuals Infected with Clade A and B Viruses

Understanding the antibody response to HIV-1 in humans that show broad neutralizing serologic activity is a crucial step in trying to reproduce such responses by vaccination. Investigating antibodies with cross clade reactivity is particularly important as these antibodies may target conserved epitopes on the HIV envelope gp160 protein. To this end we have used a clade B YU-2 gp140 trimeric antigen and single-cell antibody cloning methods to obtain 189 new anti-gp140 antibodies representing 51 independent B cell clones from the IgG memory B cells of 3 patients infected with HIV-1 clade A or B viruses and exhibiting broad neutralizing serologic activity. Our results support previous findings showing a diverse antibody response to HIV gp140 envelope protein, characterized by differentially expanded B-cell clones producing highly hypermutated antibodies with heterogenous gp140-specificity and neutralizing activity. In addition to their high-affinity binding to the HIV spike, the vast majority of the new anti-gp140 antibodies are also polyreactive. Although none of the new antibodies are as broad or potent as VRC01 or PG9, two clonally-related antibodies isolated from a clade A HIV-1 infected donor, directed against the gp120 variable loop 3, rank in the top 5% of the neutralizers identified in our large collection of 185 unique gp140-specific antibodies in terms of breadth and potency

Relationship between Exercise Capacity and Brain Size in Mammals

A great deal of experimental research supports strong associations between exercise, cognition, neurogenesis and neuroprotection in mammals. Much of this work has focused on neurogenesis in individual subjects in a limited number of species. However, no study to date has examined the relationship between exercise and neurobiology across a wide range of mammalian taxa. It is possible that exercise and neurobiology are related across evolutionary time. To test this hypothesis, this study examines the association between exercise and brain size across a wide range of mammals.Controlling for associations with body size, we examined the correlation between brain size and a proxy for exercise frequency and capacity, maximum metabolic rate (MMR; ml O(2) min(-1)). We collected brain sizes and MMRs from the literature and calculated residuals from the least-squares regression line describing the relationship between body mass and each variable of interest. We then analyzed the correlation between residual brain size and residual MMR both before and after controlling for phylogeny using phylogenetic independent contrasts. We found a significant positive correlation between maximum metabolic rate and brain size across a wide range of taxa.These results suggest a novel hypothesis that links brain size to the evolution of locomotor behaviors in a wide variety of mammalian species. In the end, we suggest that some portion of brain size in nonhuman mammals may have evolved in conjunction with increases in exercise capacity rather than solely in response to selection related to cognitive abilities

Slow Dissociation of a Charged Ligand: Analysis of the Primary Quinone QA Site of Photosynthetic Bacterial Reaction Centers

Reaction centers (RCs) are integral membrane proteins that undergo a series of electron transfer reactions during the process of photosynthesis. In the QA site of RCs from Rhodobacter sphaeroides, ubiquinone-10 is reduced, by a single electron transfer, to its semiquinone. The neutral quinone and anionic semiquinone have similar affinities, which is required for correct in situ reaction thermodynamics. A previous study showed that despite similar affinities, anionic quinones associate and dissociate from the QA site at rates ≈104 times slower than neutral quinones indicating that anionic quinones encounter larger binding barriers (Madeo, J.; Gunner, M. R. Modeling binding kinetics at the QA site in bacterial reaction centers. Biochemistry2005, 44, 10994–11004). The present study investigates these barriers computationally, using steered molecular dynamics (SMD) to model the unbinding of neutral ground state ubiquinone (UQ) and its reduced anionic semiquinone (SQ–) from the QA site. In agreement with experiment, the SMD unbinding barrier for SQ– is larger than for UQ. Multi Conformational Continuum Electrostatics (MCCE), used here to calculate the binding energy, shows that SQ– and UQ have comparable affinities. In the QA site, there are stronger binding interactions for SQ– compared to UQ, especially electrostatic attraction to a bound non-heme Fe2+. These interactions compensate for the higher SQ– desolvation penalty, allowing both redox states to have similar affinities. These additional interactions also increase the dissociation barrier for SQ– relative to UQ. Thus, the slower SQ– dissociation rate is a direct physical consequence of the additional binding interactions required to achieve a QA site affinity similar to that of UQ. By a similar mechanism, the slower association rate is caused by stronger interactions between SQ– and the polar solvent. Thus, stronger interactions for both the unbound and bound states of charged and highly polar ligands can slow their binding kinetics without a conformational gate. Implications of this for other systems are discussed

Geometric and Electronic Structures of the NiI and Methyl−NiIII Intermediates of Methyl-Coenzyme M Reductase†

ABSTRACT: Methyl-coenzyme M reductase (MCR) catalyzes the terminal step in the formation of biological methane from methyl-coenzyme M (Me-SCoM) and coenzyme B (CoBSH). The active site in MCR contains a Ni-F430 cofactor, which can exist in different oxidation states. The catalytic mechanism of methane formation has remained elusive despite intense spectroscopic and theoretical investigations. On the basis of spectroscopic and crystallographic data, the first step of the mechanism is proposed to involve a nucleophilic attack of the NiI active state (MCRred1) on Me-SCoM to form a NiIII-methyl intermediate, while computational studies indicate that the first step involves the attack of NiI on the sulfur of Me-SCoM, forming a CH3 radical and a NiII-thiolate species. In this study, a combination of Ni K-edge X-ray absorption spectroscopic (XAS) studies and density functional theory (DFT) calculations have been performed on the NiI (MCRred1), NiII (MCRred1-silent), and NiIII-methyl (MCRMe) states of MCR to elucidate the geometric and electronic structures of the different redox states. Ni K-edge EXAFS data are used to reveal a five-coordinate active site with an open upper axial coordination site in MCRred1. Ni K-pre-edge and EXAFS data and time-dependent DFT calculations unambiguously demonstrate the presence of a long Ni-C bond (∼2.04 Å) in the NiIII-methyl state of MCR. The formation and stability of this species support mechanism I, and the Ni-C bond length suggests a homolytic cleavage of the NiIII-methyl bon

A comprehensive overview of radioguided surgery using gamma detection probe technology

The concept of radioguided surgery, which was first developed some 60 years ago, involves the use of a radiation detection probe system for the intraoperative detection of radionuclides. The use of gamma detection probe technology in radioguided surgery has tremendously expanded and has evolved into what is now considered an established discipline within the practice of surgery, revolutionizing the surgical management of many malignancies, including breast cancer, melanoma, and colorectal cancer, as well as the surgical management of parathyroid disease. The impact of radioguided surgery on the surgical management of cancer patients includes providing vital and real-time information to the surgeon regarding the location and extent of disease, as well as regarding the assessment of surgical resection margins. Additionally, it has allowed the surgeon to minimize the surgical invasiveness of many diagnostic and therapeutic procedures, while still maintaining maximum benefit to the cancer patient. In the current review, we have attempted to comprehensively evaluate the history, technical aspects, and clinical applications of radioguided surgery using gamma detection probe technology