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Background: Opioid peptides, including dynorphin A, besides their analgesic action in the nervous system, exert a broad spectrum of effects on cells of the immune system, including leukocyte migration, degranulation and cytokine production. The mechanisms whereby opioid peptides induce leukocyte responses are poorly understood. The integrin Mac-1 (alpha(M)beta(2), CD11b/CD18) is

Background: Opioid peptides, including dynorphin A, besides their analgesic action in the nervous system, exert a broad spectrum of effects on cells of the immune system, including leukocyte migration, degranulation and cytokine production. The mechanisms whereby opioid peptides induce leukocyte responses are poorly understood. The integrin Mac-1 (alpha(M)beta(2), CD11b/CD18) is a multiligand receptor which mediates numerous reactions of neutrophils and monocyte/macrophages during the immune-inflammatory response. Our recent elucidation of the ligand recognition specificity of Mac-1 suggested that dynorphin A and dynorphin B contain Mac-1 recognition motifs and can potentially interact with this receptor.

Results: In this study, we have synthesized the peptide library spanning the sequence of dynorphin AB, containing dynorphin A and B, and showed that the peptides bound recombinant alpha I-M-domain, the ligand binding region of Mac-1. In addition, immobilized dynorphins A and B supported adhesion of the Mac-1-expressing cells. In binding to dynorphins A and B, Mac-1 cooperated with cell surface proteoglycans since both anti-Mac-1 function-blocking reagents and heparin were required to block adhesion. Further focusing on dynorphin A, we showed that its interaction with the alpha I-M-domain was activation independent as both the alpha 7 helix-truncated (active conformation) and helix-extended (nonactive conformation) alpha I-M-domains efficiently bound dynorphin A. Dynorphin A induced a potent migratory response of Mac-1-expressing, but not Mac-1-deficient leukocytes, and enhanced Mac-1-mediated phagocytosis of latex beads by murine IC-21 macrophages.

Conclusions: Together, the results identify dynorphins A and B as novel ligands for Mac-1 and suggest a role for the Dynorphin A-Mac-1 interactions in the induction of nonopiod receptor-dependent effects in leukocytes.

ContributorsPodolnikova, Nataly (Author) / Brothwell, Julie A. (Author) / Ugarova, Tatiana (Author) / College of Health Solutions (Contributor)
Created2015-06-03
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Description

Background: The evolution of species boundaries and the relative impact of selection and gene flow on genomic divergence are best studied in populations and species pairs exhibiting various levels of divergence along the speciation continuum. We studied species boundaries in Iberian barbels, Barbus and Luciobarbus, a system of populations and

Background: The evolution of species boundaries and the relative impact of selection and gene flow on genomic divergence are best studied in populations and species pairs exhibiting various levels of divergence along the speciation continuum. We studied species boundaries in Iberian barbels, Barbus and Luciobarbus, a system of populations and species spanning a wide degree of genetic relatedness, as well as geographic distribution and range overlap. We jointly analyze multiple types of molecular markers and morphological traits to gain a comprehensive perspective on the nature of species boundaries in these cyprinid fishes.

Results: Intraspecific molecular and morphological differentiation is visible among many populations. Genomes of all sympatric species studied are porous to gene flow, even if they are not sister species. Compared to their allopatric counterparts, sympatric representatives of different species share alleles and show an increase in all measures of nucleotide polymorphism (S, H-d, K, pi and theta). High molecular diversity is particularly striking in L. steindachneri from the Tejo and Guadiana rivers, which co-varies with other sympatric species. Interestingly, different nuclear markers introgress across species boundaries at various levels, with distinct impacts on population trees. As such, some loci exhibit limited introgression and population trees resemble the presumed species tree, while alleles at other loci introgress more freely and population trees reflect geographic affinities and interspecific gene flow. Additionally, extent of introgression decreases with increasing genetic divergence in hybridizing species pairs.

Conclusions: We show that reproductive isolation in Iberian Barbus and Luciobarbus is not complete and species boundaries are semi-permeable to (some) gene flow, as different species (including non-sister) are exchanging genes in areas of sympatry. Our results support a speciation-with-gene-flow scenario with heterogeneous barriers to gene flow across the genome, strengthening with genetic divergence. This is consistent with observations coming from other systems and supports the notion that speciation is not instantaneous but a gradual process, during which different species are still able to exchange some genes, while selection prevents gene flow at other loci. We also provide evidence for a hybrid origin of a barbel ecotype, L. steindachneri, suggesting that ecology plays a key role in species coexistence and hybridization in Iberian barbels. This ecotype with intermediate, yet variable, molecular, morphological, trophic and ecological characteristics is the local product of introgressive hybridization of L. comizo with up to three different species (with L. bocagei in the Tejo, with L. microcephalus and L. sclateri in the Guadiana). In spite of the homogenizing effects of ongoing gene flow, species can still be discriminated using a combination of morphological and molecular markers. Iberian barbels are thus an ideal system for the study of species boundaries, since they span a wide range of genetic divergences, with diverse ecologies and degrees of sympatry.

ContributorsGante, Hugo F. (Author) / Doadrio, Ignacio (Author) / Alves, Maria Judite (Author) / Dowling, Thomas (Author) / College of Liberal Arts and Sciences (Contributor)
Created2015-06-12
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Description

While expert groups often make recommendations on a range of non-controversial as well as controversial issues, little is known about how the level of expert consensus-the level of expert agreement-influences perceptions of the recommendations. This research illustrates that for non-controversial issues expert groups that exhibit high levels of agreement are

While expert groups often make recommendations on a range of non-controversial as well as controversial issues, little is known about how the level of expert consensus-the level of expert agreement-influences perceptions of the recommendations. This research illustrates that for non-controversial issues expert groups that exhibit high levels of agreement are more persuasive than expert groups that exhibit low levels of agreement. This effect is mediated by the perceived entitativity-the perceived cohesiveness or unification of the group-of the expert group. But for controversial issues, this effect is moderated by the perceivers' implicit assumptions about the group composition. When perceivers are provided no information about a group supporting the Affordable Care Act-a highly controversial piece of U.S. legislation that is divided by political party throughout the country-higher levels of agreement are less persuasive than lower levels of agreement because participants assume there were more democrats and fewer republicans in the group. But when explicitly told that the group was half republicans and half democrats, higher levels of agreement are more persuasive.

ContributorsVotruba, Ashley (Author) / Kwan, Sau (Author) / Department of Psychology (Contributor)
Created2015-03-26
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Description

Most studies on the response of socioeconomic systems to a sudden shift focus on long-term equilibria or end points. Such narrow focus forgoes many valuable insights. Here we examine the transient dynamics of regime shift on a divided population, exemplified by societies divided ideologically, politically, economically, or technologically. Replicator dynamics

Most studies on the response of socioeconomic systems to a sudden shift focus on long-term equilibria or end points. Such narrow focus forgoes many valuable insights. Here we examine the transient dynamics of regime shift on a divided population, exemplified by societies divided ideologically, politically, economically, or technologically. Replicator dynamics is used to investigate the complex transient dynamics of the population response. Though simple, our modeling approach exhibits a surprisingly rich and diverse array of dynamics. Our results highlight the critical roles played by diversity in strategies and the magnitude of the shift. Importantly, it allows for a variety of strategies to arise organically as an integral part of the transient dynamics-as opposed to an independent process-of population response to a regime shift, providing a link between the population's past and future diversity patterns. Several combinations of different populations' strategy distributions and shifts were systematically investigated. Such rich dynamics highlight the challenges of anticipating the response of a divided population to a change. The findings in this paper can potentially improve our understanding of a wide range of socio-ecological and technological transitions.

Created2015-07-10
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Description

Sensory over-responsivity, a subtype of sensory modulation disorder, is characterized by extreme negative reactions to normative sensory experiences. These over-reactions can interfere with daily activities and cause stress to children and their families. The etiology and developmental course of sensory over-responsivity is still largely unknown. We measured tactile and auditory

Sensory over-responsivity, a subtype of sensory modulation disorder, is characterized by extreme negative reactions to normative sensory experiences. These over-reactions can interfere with daily activities and cause stress to children and their families. The etiology and developmental course of sensory over-responsivity is still largely unknown. We measured tactile and auditory over-responsivity in a population-based, typically developing sample of twins (N=978) at age two years via a caregiver report temperament questionnaire and again at age seven years via a sensory over-responsivity symptom inventory. Participating twins were treated as singletons although all analyses controlled for clustering within families. Children were divided into four trajectory groups based on risk status at both ages: low symptom (N=768), remitted (N=75), late-onset (N=112), and chronic (N=24). A subset of children who screened positive for SOR in toddlerhood (N = 102) took part in a pilot study focused on sensory over-responsivity at four years of age. Children in the chronic group had more severe symptoms of sensory sensitivity at age four years, including more motion sensitivity, than the other trajectory groups. Children in the chronic group had a younger gestational age and were more likely to be low birth-weight than the low symptom group. Differences between remitted and late-onset groups and the low-symptoms group were inconsistent across measures. Sensory over-responsivity was modestly correlated across ages (r = .22 for tactile over-responsivity and r = .11 for auditory over-responsivity), but symptoms were more stable among children born prematurely or who had more fearful and less soothable temperaments. A clear implication is that assessment over development may be necessary for a valid sensory processing disorder diagnosis, and a speculative implication is that sensory over-responsivity symptoms may be etiologically heterogeneous, with different causes of transient and stable symptoms.

ContributorsVan Hulle, Carol (Author) / Lemery, Kathryn (Author) / Goldsmith, H. Hill (Author) / College of Liberal Arts and Sciences (Contributor)
Created2015-06-24
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Description

Research on how people learn shows that teaching using active learning is more effective than just lecturing. We outline four concrete ways instructors can begin to apply active learning in their teaching: backward instruction design; expecting students to learn more than facts; posing "messy" problems for students to solve; and

Research on how people learn shows that teaching using active learning is more effective than just lecturing. We outline four concrete ways instructors can begin to apply active learning in their teaching: backward instruction design; expecting students to learn more than facts; posing "messy" problems for students to solve; and expecting students to talk, write, and collaborate. Each tactic is supported with references demonstrating its efficacy and advice and links to resources for getting started with active learning.

ContributorsDolan, Erin L. (Author) / Collins, James (Author) / College of Liberal Arts and Sciences (Contributor)
Created2015-06-15
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Description

Background: The current influenza vaccines are effective against seasonal influenza, but cannot be manufactured in a timely manner for a sudden pandemic or to be cost-effective to immunize huge flocks of birds. We propose a novel influenza vaccine composing a bacterial carrier and a plasmid cargo. In the immunized subjects,

Background: The current influenza vaccines are effective against seasonal influenza, but cannot be manufactured in a timely manner for a sudden pandemic or to be cost-effective to immunize huge flocks of birds. We propose a novel influenza vaccine composing a bacterial carrier and a plasmid cargo. In the immunized subjects, the bacterial carrier invades and releases its cargo into host cells where the plasmid expresses viral RNAs and proteins for reconstitution of attenuated influenza virus. Here we aimed to construct a mouse Poll-driven plasmid for efficient production of influenza virus. Results: A plasmid was constructed to express all influenza viral RNAs and proteins. This all-in-one plasmid resulted in 10(5)-10(6) 50 % tissue culture infective dose (TCID50)/mL of influenza A virus in baby hamster kidney (BHK-21) cells on the third day post-transfection, and also reconstituted influenza virus in Madin-Darby canine kidney (MDCK) and Chinese hamster ovary (CHO) cells. A 6-unit plasmid was constructed by deleting the HA and NA cassettes from the all-in-one plasmid. Cotransfection of BHK-21 cells with the 6-unit plasmid and the two other plasmids encoding the HA or NA genes resulted in influenza virus titers similar to those produced by the 1-plasmid method. Conclusions: An all-in-one plasmid and a 3-plasmid murine Poll-driven reverse genetics systems were developed, and efficiently reconstituted influenza virus in BHK-21 cells. The all-in-one plasmid may serve as a tool to determine the factors inhibiting virus generation from a large size plasmid. In addition, we recommend a simple and robust "1 + 2" approach to generate influenza vaccine seed virus.

Created2015-06-22
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Description

Molecule-plasmon interactions have been shown to have a definite role in light propagation through optical microcavities due to strong coupling between molecular excitations and surface plasmons. This coupling can lead to macroscopic extended coherent states exhibiting increment in temporal and spatial coherency and a large Rabi splitting. Here, we demonstrate

Molecule-plasmon interactions have been shown to have a definite role in light propagation through optical microcavities due to strong coupling between molecular excitations and surface plasmons. This coupling can lead to macroscopic extended coherent states exhibiting increment in temporal and spatial coherency and a large Rabi splitting. Here, we demonstrate spatial modulation of light transmission through a single microcavity patterned on a freestanding Au film, strongly coupled to one of the most efficient energy transfer photosynthetic proteins in nature, photosystem I. Here we observe a clear correlation between the appearance of spatial modulation of light and molecular photon absorption, accompanied by a 13-fold enhancement in light transmission and the emergence of a distinct electromagnetic standing wave pattern in the cavity. This study provides the path for engineering various types of bio-photonic devices based on the vast diversity of biological molecules in nature.

ContributorsCarmeli, Itai (Author) / Cohen, Moshik (Author) / Heifler, Omri (Author) / Lilach, Yigal (Author) / Zalevsky, Zeev (Author) / Mujica, Vladimiro (Author) / Richter, Shachar (Author) / Department of Chemistry and Biochemistry (Contributor)
Created2015-06-01
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Description

The late colonial era in Uganda was not an easy time to keep families intact. Colonial officials, missionaries, and concerned East Africans offered their diagnoses of the problems and prescriptions for responding to the dilemma. In this context, Balokole Anglican revivalists articulated new patterns and ideals of family life. These

The late colonial era in Uganda was not an easy time to keep families intact. Colonial officials, missionaries, and concerned East Africans offered their diagnoses of the problems and prescriptions for responding to the dilemma. In this context, Balokole Anglican revivalists articulated new patterns and ideals of family life. These new patterns of family life were not uniform across Uganda or East Africa, but they did share common characteristics that were derived from the spiritual disciplines and religious beliefs of the Balokole revival. As such, this essay argues that the revival movement was not simply a new message of eternal salvation or primarily a form of dissent, but rather a means through which a group of African Christians sought to address quotidian domestic problems and concerns of late-colonial East Africa.

ContributorsBruner, Jason (Author) / College of Liberal Arts and Sciences (Contributor)
Created2013-11-30