Initial fixation placement in face images is driven by top-down guidance

The eyes are often inspected first and for longer period during face exploration. To examine whether this saliency of the eye region at the early stage of face inspection is attributed to its local structure properties or to the knowledge of its essence in facial communication, in this study we investigated the pattern of eye movements produced by rhesus monkeys (Macaca mulatta) as they free viewed images of monkey faces. Eye positions were recorded accurately using implanted eye coils, while images of original faces, faces with scrambled eyes, and scrambled faces except for the eyes were presented on a computer screen. The eye region in the scrambled faces attracted the same proportion of viewing time and fixations as it did in the original faces, even the scrambled eyes attracted substantial proportion of viewing time and fixations. Furthermore, the monkeys often made the first saccade towards to the location of the eyes regardless of image content. Our results suggest that the initial fixation placement in faces is driven predominantly by ‘top-down’ or internal factors, such as the prior knowledge of the location of “eyes” within the context of a face

Classical kinetic energy, quantum fluctuation terms and kinetic-energy functionals

We employ a recently formulated dequantization procedure to obtain an exact expression for the kinetic energy which is applicable to all kinetic-energy functionals. We express the kinetic energy of an N-electron system as the sum of an N-electron classical kinetic energy and an N-electron purely quantum kinetic energy arising from the quantum fluctuations that turn the classical momentum into the quantum momentum. This leads to an interesting analogy with Nelson's stochastic approach to quantum mechanics, which we use to conceptually clarify the physical nature of part of the kinetic-energy functional in terms of statistical fluctuations and in direct correspondence with Fisher Information Theory. We show that the N-electron purely quantum kinetic energy can be written as the sum of the (one-electron) Weizsacker term and an (N-1)-electron kinetic correlation term. We further show that the Weizsacker term results from local fluctuations while the kinetic correlation term results from the nonlocal fluctuations. For one-electron orbitals (where kinetic correlation is neglected) we obtain an exact (albeit impractical) expression for the noninteracting kinetic energy as the sum of the classical kinetic energy and the Weizsacker term. The classical kinetic energy is seen to be explicitly dependent on the electron phase and this has implications for the development of accurate orbital-free kinetic-energy functionals. Also, there is a direct connection between the classical kinetic energy and the angular momentum and, across a row of the periodic table, the classical kinetic energy component of the noninteracting kinetic energy generally increases as Z increases.Comment: 10 pages, 1 figure. To appear in Theor Chem Ac

Upregulation of P2Y2 receptors by retinoids in normal human epidermal keratinocytes

Retinoids, vitamin A derivatives, are important regulators of the growth and differentiation of skin cells. Although retinoids are therapeutically used for several skin ailments, little is known about their effects on P2 receptors, known to be involved in various functions in the skin. DNA array analysis showed that treatment of normal human epidermal keratinocytes (NHEKs) with all-trans-retinoic acid (ATRA), an agonist to RAR (retinoic acid receptor), enhanced the expression of mRNA for the P2Y2 receptor, a metabotropic P2 receptor that is known to be involved in the proliferation of the epidermis. The expression of other P2 receptors in NHEKs was not affected by ATRA. ATRA increased the mRNA for the P2Y2 receptor in a concentration-dependent fashion (1 nM to 1 μM). Am80, a synthesized agonist to RAR, showed a similar enhancement, whereas 9-cis-retinoic acid (9-cisRA), an agonist to RXR (retinoid X receptor), enhanced P2Y2 gene expression to a lesser extent. Ca2+ imaging analysis showed that ATRA also increased the function of P2Y2 receptors in NHEKs. Retinoids are known to enhance the turnover of the epidermis by increasing both proliferation and terminal differentiation. The DNA microarray analysis also revealed that ATRA upregulates various genes involved in the differentiation of NHEKs. Our present results suggest that retinoids, at least in part, exert their proliferative effects by upregulating P2Y2 receptors in NHEKs. This effect of retinoids may be closely related to their therapeutic effect against various ailments or aging events in skins such as over-keratinization, pigmentation and re-modeling

GPR80/99, proposed to be the P2Y15 receptor activated by adenosine and AMP, is not a P2Y receptor

The orphan receptor GPR80 (also called GPR99) was recently reported to be the P2Y15 receptor activated by AMP and adenosine and coupled to increases in cyclic AMP accumulation and intracellular Ca2+ mobilization (Inbe et al. J Biol Chem 2004; 279: 19790–9[12]). However, the cell line (HEK293) used to carry out those studies endogenously expresses A2A and A2B adenosine receptors as well as multiple P2Y receptors, which complicates the analysis of a potential P2Y receptor. To determine unambiguously whether GPR80 is a P2Y receptor subtype, HA-tagged GPR80 was either stably expressed in CHO cells or transiently expressed in COS-7 and HEK293 cells, and cell surface expression was verified by radioimmunoassay (RIA). COS-7 cells overexpressing GPR80 showed a consistent twofold increase in basal inositol phosphate accumulation. However, neither adenosine nor AMP was capable of promoting accumulation of either cyclic AMP or inositol phosphates in any of the three GPR80-expressing cells. A recent paper (He et al. Nature 2004; 429: 188–93 [15]) reported that GPR80 is a Gq-coupled receptor activated by the citric acid cycle intermediate, α-ketoglutarate. Consistent with this report, α-ketoglutarate promoted inositol phosphate accumulation in CHO and HEK293 cells expressing GPR80, and pretreatment of GPR80-expressing COS-7 cells with glutamate dehydrogenase, which converts α-ketoglutarate to glutamate, decreased basal levels of inositol phosphates. Taken together, these data demonstrate that GPR80 is not activated by adenosine, AMP or other nucleotides, but instead is activated by α-ketoglutarate. Therefore, GPR80 is not a new member of the P2Y receptor family

Computational molecular characterization of the flavonoid rutin

In this work, we make use of a model chemistry within Density Functional Theory (DFT) recently presented, which is called M05-2X, to calculate the molecular structure of the flavonoid Rutin, as well as to predict the infrared (IR) and ultraviolet (UV-Vis) spectra, the dipole moment and polarizability, the free energy of solvation in different solvents as an indication of solubility, the HOMO and LUMO orbitals, and the chemical reactivity parameters that arise from Conceptual DFT. The calculated values are compared with the available experimental data for this molecule as a means of validation of the used model chemistry

An exploration of the relationships among facial dimensions, age, sex, dominance status and personality in rhesus macaques (Macaca mulatta)

Aspects of personality in nonhuman primates have been linked to health, social relationships, and life history outcomes. In humans as well as nonhuman primates, facial morphology is associated with assertiveness, aggression, and measures of dominance status. In this study we aimed to examine the relationship among facial morphology, age, sex, dominance status, and ratings on the personality dimensions Confidence, Openness, Assertiveness, Friendliness, Activity, and Anxiety in rhesus macaques (Macaca mulatta). We measured facial width-to-height ratio (fWHR) and lower-height/full-height ratio (fLHFH) using photographs from 109 captive rhesus macaques, which observers also assessed for dominance status and personality, and explored the associations among facial morphology, age, sex, dominance status, and personality. fWHR and fLHFH personality associations depended on age category: Assertiveness was associated with higher fWHR and fLHFH, and Confidence was associated with lower fWHR and fLHFH, but all these associations were consistent only in individuals <8 yr. of age. We found fWHR and fLHFH to not be consistently associated with sex or dominance status; compared to younger individuals, we found few associations with fWHR and fLHFH for individuals older than 8 yr., which may be due to limited sample size. Our results indicate that in macaques <8 yr. old, facial morphology is associated with the Assertiveness and Confidence personality dimensions, which is consistent with results suggesting a relationship between fWHR and trait aggression in humans and assertiveness in brown capuchins, all of which implies that fWHR might be a cue to assertive and aggressive traits

E pluribus plurima: Multidimensional indices and clinical phenotypes in COPD

as the picture of COPD becomes more complex and the results from large studies generate the need of further research, it is clear the close link between the definition of clinical phenotypes and the validation of either single or multidimensional indices

Grafted Human Embryonic Progenitors Expressing Neurogenin-2 Stimulate Axonal Sprouting and Improve Motor Recovery after Severe Spinal Cord Injury

7 p.Background: Spinal cord injury (SCI) is a widely spread pathology with currently no effective treatment for any symptom. Regenerative medicine through cell transplantation is a very attractive strategy and may be used in different non-exclusive ways to promote functional recovery. We investigated functional and structural outcomes after grafting human embryonic neural progenitors (hENPs) in spinal cord-lesioned rats.Methods and Principal Findings: With the objective of translation to clinics we have chosen a paradigm of delayed grafting, i.e., one week after lesion, in a severe model of spinal cord compression in adult rats. hENPs were either naive or engineered to express Neurogenin 2 (Ngn2). Moreover, we have compared integrating and non-integrating lentiviral vectors, since the latter present reduced risks of insertional mutagenesis. We show that transplantation of hENPs transduced to express Ngn2 fully restore weight support and improve functional motor recovery after severe spinal cord compression at thoracic level. This was correlated with partial restoration of serotonin innervations at lumbar level, and translocation of 5HT1A receptors to the plasma membrane of motoneurons. Since hENPs were not detectable 4 weeks after grafting, transitory expression of Ngn2 appears sufficient to achieve motor recovery and to permit axonal regeneration. Importantly, we also demonstrate that transplantation of naive hENPs is detrimental to functional recovery.Conclusions and Significance: Transplantation and short-term survival of Ngn2-expressing hENPs restore weight support after SCI and partially restore serotonin fibers density and 5HT1A receptor pattern caudal to the lesion. Moreover, grafting of naive-hENPs was found to worsen the outcome versus injured only animals, thus pointing to the possible detrimental effect of stem cell-based therapy per se in SCI. This is of major importance given the increasing number of clinical trials involving cell grafting developed for SCI patients.This study was supported by the European Union FP6 "RESCUE" STREP; the "Institut pour la Recherche sur la Moelle Epiniere"; the "Academie de Medecine"; the "Societe Francaise de Neurochirurgie"; "Verticale" and the "Association Demain Debout Aquitaine". The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Linking Microscopic Spatial Patterns of Tissue Destruction in Emphysema to Macroscopic Decline in Stiffness Using a 3D Computational Model

Pulmonary emphysema is a connective tissue disease characterized by the progressive destruction of alveolar walls leading to airspace enlargement and decreased elastic recoil of the lung. However, the relationship between microscopic tissue structure and decline in stiffness of the lung is not well understood. In this study, we developed a 3D computational model of lung tissue in which a pre-strained cuboidal block of tissue was represented by a tessellation of space filling polyhedra, with each polyhedral unit-cell representing an alveolus. Destruction of alveolar walls was mimicked by eliminating faces that separate two polyhedral either randomly or in a spatially correlated manner, in which the highest force bearing walls were removed at each step. Simulations were carried out to establish a link between the geometries that emerged and the rate of decline in bulk modulus of the tissue block. The spatially correlated process set up by the force-based destruction lead to a significantly faster rate of decline in bulk modulus accompanied by highly heterogeneous structures than the random destruction pattern. Using the Karhunen-Loève transformation, an estimator of the change in bulk modulus from the first four moments of airspace cell volumes was setup. Simulations were then obtained for tissue destruction with different idealized alveolar geometry, levels of pre-strain, linear and nonlinear elasticity assumptions for alveolar walls and also mixed destruction patterns where both random and force-based destruction occurs simultaneously. In all these cases, the change in bulk modulus from cell volumes was accurately estimated. We conclude that microscopic structural changes in emphysema and the associated decline in tissue stiffness are linked by the spatial pattern of the destruction process

A Rapid and Sensitive Method for Measuring NAcetylglucosaminidase Activity in Cultured Cells

A rapid and sensitive method to quantitatively assess N-acetylglucosaminidase (NAG) activity in cultured cells is highly desirable for both basic research and clinical studies. NAG activity is deficient in cells from patients with Mucopolysaccharidosis type IIIB (MPS IIIB) due to mutations in NAGLU, the gene that encodes NAG. Currently available techniques for measuring NAG activity in patient-derived cell lines include chromogenic and fluorogenic assays and provide a biochemical method for the diagnosis of MPS IIIB. However, standard protocols require large amounts of cells, cell disruption by sonication or freeze-thawing, and normalization to the cellular protein content, resulting in an error-prone procedure that is material- and time-consuming and that produces highly variable results. Here we report a new procedure for measuring NAG activity in cultured cells. This procedure is based on the use of the fluorogenic NAG substrate, 4- Methylumbelliferyl-2-acetamido-2-deoxy-alpha-D-glucopyranoside (MUG), in a one-step cell assay that does not require cell disruption or post-assay normalization and that employs a low number of cells in 96-well plate format. We show that the NAG one-step cell assay greatly discriminates between wild-type and MPS IIIB patient-derived fibroblasts, thus providing a rapid method for the detection of deficiencies in NAG activity. We also show that the assay is sensitive to changes in NAG activity due to increases in NAGLU expression achieved by either overexpressing the transcription factor EB (TFEB), a master regulator of lysosomal function, or by inducing TFEB activation chemically. Because of its small format, rapidity, sensitivity and reproducibility, the NAG one-step cell assay is suitable for multiple procedures, including the high-throughput screening of chemical libraries to identify modulators of NAG expression, folding and activity, and the investigation of candidate molecules and constructs for applications in enzyme replacement therapy, gene therapy, and combination therapies