Extending perspective taking to nonhuman animals and artificial entities

Perspective taking can have positive effects in a range of intergroup contexts. In two experiments, we tested whether these effects generalize to two yet-to-be-studied nonhuman groups: animals and intelligent artificial entities. We found no overall effects of either taking the perspective of a farmed pig or an artificial entity on moral attitudes, compared to instructions to stay objective and a neutral condition. However, in both studies, mediation analysis indicated that perspective taking positively affected moral attitudes via empathic concern and self-other overlap, supporting two mechanisms well-established in the literature. The lack of overall effects may be partly explained by positive effects of staying objective on moral attitudes that offset the positive effects of perspective taking via empathic concern and self-other overlap. These findings suggest that perspective taking functions differently in the context of nonhuman groups relative to typical intergroup contexts. We consider this an important area for future research

Assisted Reproduction Versus Spontaneous Conception: A Comparison of the Developmental Outcomes in Twins

The use of assisted reproductive technology is increasing rapidly. Research, although sparse, has resulted in inconsistent findings as to the developmental prognosis for infants conceived by assisted reproductive techniques such as in vitro fertilization and the use of fertility drugs. In the present study, the authors compared twins who were spontaneously conceived with those who were conceived through assisted reproductive technology. The authors found differences in birth weight and gestational age. Infants conceived by assisted reproductive technology fared worse than did those who were spontaneously conceived. The authors found no differences between the groups in mental development at 24 months of age, but they found evidence of differences in physical development. Implications of the findings are discussed

Advancing Science through Conversations: Bridging the Gap between Blogs and the Academy

Blogs have stormed the Internet, providing an interactive medium for rapid and wide-reaching information dispersal. But is there a place for blogs in academia

Sphingosine-1-phosphate inhibits vascular smooth muscle cell migration by activating Gα₁₂ and RhoA

Due to the character of the original source materials and the nature of batch digitization, quality control issues may be present in this document. Please report any quality issues you encounter to [email protected], referencing the URI of the item.Includes bibliographical references (leaves 24-27).Angiogenesis, the formation of new blood vessels, is important in growth, healing, and disease. Sphingosine-1-phosphate (S1P) is a lysophospholipid with potent angiogenic effects. One of these effects is its regulation of cellular migration, an early step in angiogenesis. S1P exerts contradictory effects on different types of vascular cells, strongly inducing endothelial cell (EC) migration while strongly inhibiting vascular smooth muscle cells (VSMC) migration. Here, we demonstrate that S1P inhibits the migration of VSMCs by activating G[α]₁₂ and RhoA. S1P abolished the migration of VSMCs in response to platelet-derived growth factor (PDGF), a potent stimulator of VSMC migration. PDGF strongly induced the formation of lamellipodia, which are membrane ruffles associated with cell migration. S1P eliminated these and induced the formation of stress fibers, which are actin cytoskeletal structures that stabilize the cell. The members of the Rho family of small GTPases regulate cytoskeletal morphology and function. Rac1 induces lamellipodia, RhoA induces stress fibers, and Cdc42 induces filopodia, which are small finger-like membrane spikes. We introduced dominant-negative (DN) and constitutively active (CA) mutants of the Rho GTPases into VSMCs using adenoviral vectors. The results indicated that S1P inhibits VSMC migration by activating RhoA. RhoA activation was also demonstrated directly using a RhoA pull-down assay. S1P exerts its cellular effects by activating the endothelial differentiation gene G-protein-coupled receptors, which initiate signaling pathways by activating different G[α] subunits of heterotrimeric G proteins. To determine which G[α] subunit S1P activates in order to activate RhoA, we introduced DN and CA mutants of G[α]₁₂ and G[α]₁₃ into VSMCs through adenoviral vectors. The results indicated that S1P activates RhoA by activating G[α]₁₂. These results are important because they further elucidate some of the key signaling pathways regulating angiogenesis. When angiogenesis begins, ECs migrate in response to S1P and other factors. Interestingly, our new data suggest that S1P may prevent VSMCs from interfering with early EC tube assembly, by inhibiting VSMC migration through selective activation of G[α]₁₂ and RhoA. Later, after the ECs have established a network of capillary tubes, they secrete additional factors, such as PDGF, which attract VSMCs to them, allowing mature blood vessels to form

Design and Construction of a Molecular Beamline for Cluster Catalysis Studies

Metal and metal oxide nanoparticles are widely used in heterogeneous catalysis. In order to determine how these catalysts function and in order to find new catalysts, model systems can be used to provide experimental and computational insight. One such model system is a cluster which contains <100 atoms allowing for ease of calculation. In this work a molecular beamline was constructed in order to produce a wide range of these clusters and control their composition on an atom-by-atom level. These clusters could then be deposited onto a substrate in vacuum and studied via multiple techniques including TPD, XPS, UPS, LEED, and STM, allowing for the study of not only the cluster’s composition but their reactivity to a range of reactants in a range of reaction environments. In the process of designing the instrument, novel tools and parts were developed and manufactured to push the capabilities of the instrument forward and are discussed in detail. The instrument was tested and found to meet the three design goals of a molecular beamline that can 1) produce a large range of clusters varying in size and composition of a magnitude that can be deposited and studied in a timely fashion, 2) mass select the clusters with a resolution capable of resolving the elements in the cluster, and 3) bring to bear a variety of analytical techniques to study the cluster’s composition and catalytic capabilities

Consciousness Semanticism: A Precise Eliminativist Theory of Consciousness

Many philosophers and scientists claim that there is a ‘hard problem of consciousness’, that qualia, phenomenology, or subjective experience cannot be fully understood with reductive methods of neuroscience and psychology, and that there is a fact of the matter as to ‘what it is like’ to be conscious and which entities are conscious (Chalmers, 1995). Eliminativism and related views such as illusionism argue against this; they claim that consciousness does not exist in the ways implied by everyday or scholarly language. However, this debate has largely consisted of each side jousting analogies and intuitions against the other. Both sides remain unconvinced. To break through this impasse, I present _consciousness semanticism_, a novel eliminativist theory that sidesteps analogy and intuition. Instead, it is based on a direct, formal argument drawing from the tension between the vague semantics in definitions of consciousness such as ‘what it is like’ to be an entity (Nagel, 1975) and the precise meaning implied by questions such as, ‘Is this entity conscious?’ I argue that semanticism naturally extends to erode realist notions of other philosophical concepts, such as morality and free will. Formal argumentation from precise semantics exposes these as pseudo-problems and removes their apparent mysteriousness and intractability

Tumor cell invasion of collagen matrices requires coordinate lipid agonist-induced G-protein and membrane-type matrix metalloproteinase-1-dependent signaling

BACKGROUND: Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are bioactive lipid signaling molecules implicated in tumor dissemination. Membrane-type matrix metalloproteinase 1 (MT1-MMP) is a membrane-tethered collagenase thought to be involved in tumor invasion via extracellular matrix degradation. In this study, we investigated the molecular requirements for LPA- and S1P-regulated tumor cell migration in two dimensions (2D) and invasion of three-dimensional (3D) collagen matrices and, in particular, evaluated the role of MT1-MMP in this process. RESULTS: LPA stimulated while S1P inhibited migration of most tumor lines in Boyden chamber assays. Conversely, HT1080 fibrosarcoma cells migrated in response to both lipids. HT1080 cells also markedly invaded 3D collagen matrices (~700 μm over 48 hours) in response to either lipid. siRNA targeting of LPA(1 )and Rac1, or S1P(1), Rac1, and Cdc42 specifically inhibited LPA- or S1P-induced HT1080 invasion, respectively. Analysis of LPA-induced HT1080 motility on 2D substrates vs. 3D matrices revealed that synthetic MMP inhibitors markedly reduced the distance (~125 μm vs. ~45 μm) and velocity of invasion (~0.09 μm/min vs. ~0.03 μm/min) only when cells navigated 3D matrices signifying a role for MMPs exclusively in invasion. Additionally, tissue inhibitors of metalloproteinases (TIMPs)-2, -3, and -4, but not TIMP-1, blocked lipid agonist-induced invasion indicating a role for membrane-type (MT)-MMPs. Furthermore, MT1-MMP expression in several tumor lines directly correlated with LPA-induced invasion. HEK293s, which neither express MT1-MMP nor invade in the presence of LPA, were transfected with MT1-MMP cDNA, and subsequently invaded in response to LPA. When HT1080 cells were seeded on top of or within collagen matrices, siRNA targeting of MT1-MMP, but not other MMPs, inhibited lipid agonist-induced invasion establishing a requisite role for MT1-MMP in this process. CONCLUSION: LPA is a fundamental regulator of MT1-MMP-dependent tumor cell invasion of 3D collagen matrices. In contrast, S1P appears to act as an inhibitory stimulus in most cases, while stimulating only select tumor lines. MT1-MMP is required only when tumor cells navigate 3D barriers and not when cells migrate on 2D substrata. We demonstrate that tumor cells require coordinate regulation of LPA/S1P receptors and Rho GTPases to migrate, and additionally, require MT1-MMP in order to invade collagen matrices during neoplastic progression

A rigid disulfide-linked nitroxide side chain simplifies the quantitative analysis of PRE data

The measurement of 1H transverse paramagnetic relaxation enhancement (PRE) has been used in biomolecular systems to determine long-range distance restraints and to visualize sparsely-populated transient states. The intrinsic flexibility of most nitroxide and metalchelating paramagnetic spin-labels, however, complicates the quantitative interpretation of PREs due to delocalization of the paramagnetic center. Here, we present a novel, disulfide-linked nitroxide spin label, R1p, as an alternative to these flexible labels for PRE studies. When introduced at solvent-exposed α-helical positions in two model proteins, calmodulin (CaM) and T4 lysozyme (T4L), EPR measurements show that the R1p side chain exhibits dramatically reduced internal motion compared to the commonly used R1 spin label (generated by reacting cysteine with the spin labeling compound often referred to as MTSL). Further, only a single nitroxide position is necessary to account for the PREs arising from CaM S17R1p, while an ensemble comprising multiple conformations is necessary for those observed for CaM S17R1. Together, these observations suggest that the nitroxide adopts a single, fixed position when R1p is placed at solvent-exposed α-helical positions, greatly simplifying the interpretation of PRE data by removing the need to account for the intrinsic flexibility of the spin label

Coregulation of vascular tube stabilization by endothelial cell TIMP-2 and pericyte TIMP-3

The endothelial cell (EC)–derived tissue inhibitor of metalloproteinase-2 (TIMP-2) and pericyte-derived TIMP-3 are shown to coregulate human capillary tube stabilization following EC–pericyte interactions through a combined ability to block EC tube morphogenesis and regression in three-dimensional collagen matrices. EC–pericyte interactions strongly induce TIMP-3 expression by pericytes, whereas ECs produce TIMP-2 in EC–pericyte cocultures. Using small interfering RNA technology, the suppression of EC TIMP-2 and pericyte TIMP-3 expression leads to capillary tube regression in these cocultures in a matrix metalloproteinase-1 (MMP-1)–, MMP-10–, and ADAM-15 (a disintegrin and metalloproteinase-15)–dependent manner. Furthermore, we show that EC tube morphogenesis (lumen formation and invasion) is primarily controlled by the TIMP-2 and -3 target membrane type (MT) 1 MMP. Additional targets of these inhibitors include MT2-MMP and ADAM-15, which also regulate EC invasion. Mutagenesis experiments reveal that TIMP-3 requires its proteinase inhibitory function to induce tube stabilization. Overall, these data reveal a novel role for both TIMP-2 and -3 in the pericyte-induced stabilization of newly formed vascular networks that are predisposed to undergo regression and reveal specific molecular targets of the inhibitors regulating these events