290 research outputs found
Ecomorphological variation among redbreast sunfish populations of the South-Eastern United States
Individual populations of a species will morphologically adapt to their surrounding environment. It has been noted in the past that when species are placed under similar environmental conditions, they will evolve similar morphological structures and shape variation to overcome those obstacles. Redbreast sunfish (Lepomis auritus) were sampled from three different ecoregions (mountainous, Piedmont, and coastal plain) of 4 different isolated river basins in the southeastern North America. It was hypothesized that across basins, populations would show convergent morphological adaptations to mountain, piedmont, and coastal plain condition. I indexed using site elevation as an independent variable, serving as a proxy for ecoregion. I measured 9 morphological variables on 146 preserved redbreast specimens from 32 sites spanning all basins and ecoregions. I used a principal components analysis to visualize the variation among basins and ecoregions and generalized linear mixed models to test hypothesized relationships between each morphological variable and elevation. It was found that mountainous redbreast have smaller eyes, shorter caudal peduncles, and a rounder head shape. This may be due to the clearer waters of mountain streams and the behavior of waiting in the littoral zone as opposed to the turbulent center. However, several traits did not consistently vary with ecoregion in the hypothesized way, suggesting that basin effect cannot be ignored on redbreast morphology
pH-dependent mechanism of nitric oxide release in nitrophorins 2 and 4
Nitrophorins are NO carrier proteins that transport and release NO through a pH-dependent conformational change. They bind NO tightly in a low pH environment and release it in a higher pH environment. Experimental evidence shows that the increase in the NO dissociation equilibrium constant, K d, is due mainly to an increase in the NO release rate. Structural and kinetic data strongly suggest that NPs control NO escape by modulating its migration from the active site to the solvent through a pH-dependent conformational change. NP2 and NP4 are two representative proteins of the family displaying a 39% overall sequence identity, and interestingly, NP2 releases NO slower than NP4. The proposal that NPs' NO release relies mainly on the NO escape rate makes NPs a very peculiar case among typical heme proteins. The connection between the pH-dependent conformational change and ligand release mechanism is not fully understood and the structural basis for the pH induced structural transition and the different NO release patterns in NPs are unresolved, yet interesting issues. In this work, we have used state of the art molecular dynamics simulations to study the NO escape process in NP2 and NP4 in both the low and high pH states. Our results show that both NPs modulate NO release by switching between a "closed" conformation in a low pH environment and an "open" conformation at higher pH. In both proteins, the change is caused by the differential protonation of a common residue Asp30 in NP4 and Asp29 in NP2, and the NO escape route is conserved. Finally, our results show that, in NP2, the conformational change to the "open" conformation is smaller than that for NP4 which results in a higher barrier for NO release.Fil: Swails, Jason M.. University of Florida; Estados UnidosFil: Meng, Yilin. University of Florida; Estados UnidosFil: Walker, F. Ann. University of Arizona; Estados UnidosFil: Marti, Marcelo Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Estrin, Dario Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Roitberg, Adrián. University of Florida; Estados Unido
Analysis of Opioid Prescription Patterns and Postoperative Opioid Use in Opioid-Naïve Patients Undergoing Elective Lumbar Spine Surgery
Title: Analysis of Opioid Prescription Patterns and Postoperative Opioid Use in Opioid-Naïve Patients Undergoing Elective Lumbar Spine Surgery
Background: Post-operative opioid prescribing patterns after elective spine surgery is a growing topic of concern, as over-prescribing can lead to potential medication dependence, while under-prescribing can lead to inadequate pain management.
Objective: The primary objective was to develop prescribing guidelines based upon the amount of opioids used in the first 2 weeks after lumbar spine surgery by 80% of patients.
Methods: Utilizing a prospective study design, opioid-naïve patients undergoing elective lumbar spine surgery at our institution were identified each week and preoperatively consented for study participation. Opioid naivete was defined as lack of opioid use at least 1 month prior to the scheduled surgical procedure. At 2 weeks postoperatively, enrolled patients completed a telephone survey questionnaire, which assessed remaining opioid prescription pill count, need for medication refill, and subjective patient satisfaction with opioid dosing. Subsequently, patient charts were retrospectively reviewed for patient demographic and medical co-morbidity data. Univariate two group comparisons were performed using t-tests for continuous variables, and using chi-square, or Fisher’s tests if cell counts are \u3c5 for categorical variables. We then looked at the distribution of MMEs in each cohort in order to determine the opioid needs of 80% of the patient population.
Results: A total of 53 opioid-naïve spine surgery patients were included for analysis, of which 23 underwent fusion surgery and 30 underwent non-fusion surgery. Baseline demographics and co-morbidities did not significantly vary between groups. For the fusion group, analysis revealed that an MME of 90 would meet the opioid requirements for 80% of patients. In this group, 60% of fusion patients were under-prescribed opioids, while 27% of patients were over-prescribed. For the non-fusion group, an MME of 45 was determined to meet the opioid requirements of 80% of patients. In this group, 61% of non-fusion patients were overprescribed opioids, while 22% were under prescribed.
Conclusions: Amongst opioid-naïve patients who underwent elective lumber spine surgery, patients in the lumbar fusion group were generally under-prescribed postoperative opioids, while patients in the non-fusion groups were over-prescribed. This discrepancy suggests that spine surgeons must account for the procedure type (i.e., fusion vs non-fusion) when prescribing opiates postoperatively in opioid-naïve patients, given patients undergoing lumbar fusion may require a larger MME than non-fusion patients.
Keywords: opioid-naïve; lumbar spine surgery; fusion; postoperative opioid use; MM
The Bright Side of Dark Matter
We show that it is not possible in the absence of dark matter to construct a
four-dimensional metric that explains galactic observations. In particular, by
working with an effective potential it is shown that a metric which is
constructed to fit flat rotation curves in spiral galaxies leads to the wrong
sign for the bending of light i.e. repulsion instead of attraction. Hence,
without dark matter the motion of particles on galactic scales cannot be
explained in terms of geodesic motion on a four- dimensional metric. This
reveals a new bright side to dark matter: it is indispensable if we wish to
retain the cherished equivalence principle.Comment: 7 pages, latex, no figures. Received an honorable mention in the 1999
Gravity research Foundation Essay Competition. Submitted to Phys. Rev. Let
Process and Context in Choice Models
We develop a general framework that extends choice models by including an explicit representation of the process and context of decision making. Process refers to the steps involved in decision making. Context refers to factors affecting the process, focusing in this paper on social networks. The extended choice framework includes more behavioral richness through the explicit representation of the planning process preceding an action and its dynamics and the effects of context (family, friends, and market) on the process leading to a choice, as well as the inclusion of new types of subjective data in choice models. We discuss the key issues involved in applying the extended framework, focusing on richer data requirements, theories, and models, and present three partial demonstrations of the proposed framework. Future research challenges include the development of more comprehensive empirical tests of the extended modeling framework
Modulation of integrin antagonist signaling by ligand binding of the heparin-binding domain of vitronectin to the αVβ3 integrin
The interaction between the arginine glycine and aspartic acid motif (RGD) of integrin ligands such as vitronectin and the integrin receptor αVβ3 in mediating cell attachment has been well described. Similarly, the ability of disintegrins, small RGD containing peptides, to inhibit cell attachment and other cellular processes has also been studied extensively. Recently, we characterized a second site of interaction between vitronectin and its integrin partner. We determined that amino acids within the heparin binding domain of vitronectin bind to a cysteine loop (C-loop) region of β3 and that this interaction is required for the positive effects of αVβ3 ligand occupancy on IGF-I signaling in smooth muscle cells. In this study we examine the signaling events activated following ligand binding of disintegrins to the αVβ3 and the ability of these signals to be regulated by binding of the heparin binding domain of vitronectin. We demonstrate that disintegrin ligand binding activates a series of events including the sequential activation of the tyrosine kinases c-Src and Syk. This leads to the activation of calpain and the cleavage of the β3 cytoplasmic tail. Addition of vitronectin or a peptide homologous to the heparin binding domain inhibited activation of this pathway
A New Glycan-Dependent CD4-Binding Site Neutralizing Antibody Exerts Pressure on HIV-1 In Vivo
The CD4 binding site (CD4bs) on the envelope glycoprotein is a major site of vulnerability that is conserved among different HIV-1 isolates. Many broadly neutralizing antibodies (bNAbs) to the CD4bs belong to the VRC01 class, sharing highly restricted origins, recognition mechanisms and viral escape pathways. We sought to isolate new anti-CD4bs bNAbs with different origins and mechanisms of action. Using a gp120 2CC core as bait, we isolated antibodies encoded by IGVH3-21 and IGVL3-1 genes with long CDRH3s that depend on the presence of the N-linked glycan at position-276 for activity. This binding mode is similar to the previously identified antibody HJ16, however the new antibodies identified herein are more potent and broad. The most potent variant, 179NC75, had a geometric mean IC_(80) value of 0.42 μg/ml against 120 Tier-2 HIV-1 pseudoviruses in the TZM.bl assay. Although this group of CD4bs glycan-dependent antibodies can be broadly and potently neutralizing in vitro, their in vivo activity has not been tested to date. Here, we report that 179NC75 is highly active when administered to HIV-1-infected humanized mice, where it selects for escape variants that lack a glycan site at position-276. The same glycan was absent from the virus isolated from the 179NC75 donor, implying that the antibody also exerts selection pressure in humans
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