Ectodysplasin/NF-κB Promotes Mammary Cell Fate via Wnt/β-catenin Pathway.

Mammary gland development commences during embryogenesis with the establishment of a species typical number of mammary primordia on each flank of the embryo. It is thought that mammary cell fate can only be induced along the mammary line, a narrow region of the ventro-lateral skin running from the axilla to the groin. Ectodysplasin (Eda) is a tumor necrosis factor family ligand that regulates morphogenesis of several ectodermal appendages. We have previously shown that transgenic overexpression of Eda (K14-Eda mice) induces formation of supernumerary mammary placodes along the mammary line. Here, we investigate in more detail the role of Eda and its downstream mediator transcription factor NF-κB in mammary cell fate specification. We report that K14-Eda mice harbor accessory mammary glands also in the neck region indicating wider epidermal cell plasticity that previously appreciated. We show that even though NF-κB is not required for formation of endogenous mammary placodes, it is indispensable for the ability of Eda to induce supernumerary placodes. A genome-wide profiling of Eda-induced genes in mammary buds identified several Wnt pathway components as potential transcriptional targets of Eda. Using an ex vivo culture system, we show that suppression of canonical Wnt signalling leads to a dose-dependent inhibition of supernumerary placodes in K14-Eda tissue explants.

Patterns of variability of retinol levels in a harbour porpoise population from an unpolluted environment

Organochlorine compounds (OC) are known to induce vitamin A (retinoids) deficiency in mammals, which may be associated with impairment of immunocompetence, reproduction and growth. This makes retinoids a potentially useful biomarker of organochlorine impact on marine mammals. However, use of retinoids as a biomarker requires knowledge about its intrapopulation patterns of variation in natural conditions, information which is not currently available. We investigated these patterns in a cetacean population living in an unpolluted environment. 100 harbour porpoises Phocoena phocoena from West Greenland were sampled during the 1995 hunting season. Sex, age, morphometrics, nutritive condition, and retinol (following saponification) and OC levels in blubber were determined for each individual. OC levels found were extremely low and therefore considered unlikely to affect the population adversely: mean blubber concentrations, expressed on an extractable basis, were 2.04 (SD = 1.1) ppm for PCBs and 2.76 (SD = 1.66) ppm for tDDT. The mean blubber retinol concentration for the overall population was 59.66 (SD = 45.26) mu g g(-1). Taking into account the high contribution of blubber to body mass, blubber constitutes a significant body site for retinoid deposition in harbour porpoises. Retinol concentrations did not differ significantly between geographical regions or sexes, but they did correlate significantly (p <0.001) with age. Body condition, measured by determining the lipid content of the blubber, did not have a significant effect on retinol levels but the individuals examined were considered to be in an overall good nutritive condition. It is concluded that measurement of retinol concentrations in blubber samples is feasible and has a potential for use as a biomarker of organochlorine exposure in cetaceans. However, in order to do so, biological information, particularly age, is critical for the correct assessment of physiological impact

Ejaculate Characteristics Depend on Social Environment in the Horse (Equus caballus).

Sperm competition theory predicts semen characteristics to be affected by the social environment. We used the polygamous horse (Equus caballus) to experimentally study within-subject plasticity in response to different social environments. Stallions were sequentially exposed, over a period of 8 weeks each, to other stallions and then singly to mares, or vice versa (in adjacent boxes separated by grills). Ejaculates were collected to determine semen characteristics. Highest sperm numbers were found in stallions that were first exposed to other stallions and then to mares, while lowest sperm numbers were observed in stallions that had been exposed to mares but not yet to other stallions. One of three sperm velocity measures (curvilinear velocity) was consistently elevated in stallions that were first exposed to stallions and then to mares. Sperm number after exposure to mares and curvilinear sperm velocity after exposure to stallions were both positively correlated to average blood testosterone levels during the corresponding period of exposure. We conclude that ejaculate characteristics are plastic traits affected by the social environment in horses.

Fate of cadmium in rat renal tubules: a micropuncture study.

Free-flow micropuncture was carried out in superficial nephrons of Munich-Wistar type rats infused acutely with Cd acetate (CdA) or Cd-DTPA (141 microM Cd). Fluid obtained from Bowman's space (BS) or end-proximal tubule sites was analyzed for Cd and inulin. The fluid/plasma Cd concentration ratio in BS averaged 0.2 and 1.0 during CdA and Cd-DTPA infusions, respectively. End-proximal tubule fractional excretion of Cd during CdA infusion averaged 0.34. Previous administration of CdA (1.0 mg/kg, 48 hr before micropuncture) increased the level of circulating Cd-metallothioneins, as measured by radioimmunoassay, but did not affect the luminal tubular uptake of Cd during CdA infusion. No net transepithelial movement of Cd-DTPA was measured. It is concluded that Cd ultrafiltered during inorganic Cd administration is taken up to a large extent by the convoluted part of proximal tubules.

Concurrent : Easy to use Python computing environment

Concurrent aims to be a different type of task distribution system compared to what MPI like system do. It adds a simple but powerful application abstraction layer to distribute the logic of an entire application onto a swarm of clusters holding similarities with volunteer computing systems. Traditional task distributed systems will just perform simple tasks onto the distributed system and wait for results. Concurrent goes one step further by letting the tasks and the application decide what to do. The programming paradigm is then totally async without any waits for results and based on notifications once a computation has been performed.

Fate of cadmium in rat renal tubules: a microinjection study.

109Cd was injected into the lumen of superficial proximal or distal tubules of rat kidneys, and recovery in the pelvic urine from the ipsilateral kidney was measured. Fractional recovery of labeled inulin always exceeded 90%. About 70% of injected inorganic Cd (CdCl2) was taken up by the epithelium of proximal tubules, while more than 90% of the injected amount was recovered after distal microinjection. The proximal fractional Cd uptake of a 1:1 (molar) Cd-L-cysteine complex was 82%, but was below 60% for a 5-10:1 molar ratio of cysteine:Cd. The chelate Cd-pentetic acid was recovered in final urine nearly quantitatively after proximal or distal microinjection. Fractional uptake of 109Cd from a Cd-metallothionein (Mt) complex, following proximal microinjection, ranged between 17 (Cd-Mt 0.19 mM) and 8% (Cd-Mt 1.5 mM). It is concluded that luminal Cd uptake by the tubular epithelium depends markedly on the chemical form of Cd and, when present, occurs mostly or exclusively in proximal tubules.

Regional differences of physical activity and sedentary behaviour in Swiss children are not explained by socio-demographics or the built environment.

OBJECTIVE: We evaluated whether regional differences in physical activity (PA) and sedentary behaviour (SB) existed along language boundaries within Switzerland and whether potential differences would be explained by socio-demographics or environmental characteristics. METHODS: We combined data of 611 children aged 4 to 7 years from four regional studies. PA and SB were assessed by accelerometers. Information about the socio-demographic background was obtained by questionnaires. Objective neighbourhood attributes could be linked to home addresses. Multivariate regression models were used to test associations between PA and SB and socio-demographic characteristics and neighbourhood attributes. RESULTS: Children from the German compared to the French-speaking region were more physically active and less sedentary (by 10-15 %, p < 0.01). Although German-speaking children lived in a more favourable environment and a higher socioeconomic neighbourhood (differences p < 0.001), these characteristics did not explain the differences in PA behaviour between French and German speaking. CONCLUSIONS: Factors related to the language region, which might be culturally rooted were among the strongest correlates of PA and SB among Swiss children, independent of individual, social and environmental factors.

The El Masnou Infralittoral sedimentary environment (Barcelona province, NW Mediterranean Sea): morphology and Holocene seismic stratigraphy

A detailed analysis of the morphology and the Holocene seismic and sequence stratigraphy and architecture of the infralittoral sedimentary environment of the El Masnou coast (Catalonia, NW Mediterranean Sea) was carried out using multibeam bathymetry and GeoPulse seismic data. This environment extends down to 26-30 m water depth, and is defined morphologically by two depositional wedges whose seafloor is affected by erosive furrows, slides, fields of large- and small-scale wavy bedforms, and dredging trenches and pits. Erosive terraces are also identified in the transition domain toward the inner continental shelf. The Holocene stratigraphy of the infralittoral environment is defined by two major seismic sequences (lower and upper), each one formed by internal seismic units. The sequences and units are characterised by downlapping surfaces made up of deposits formed by progradation of coastal lithosomes. The stratigraphy and stratal architecture, displaying a retrogradational arrangement with progradational patterns of minor order, were controlled by different sea-level positions. The stratigraphic division represents the coastal response to the last fourth-order transgressive and highstand conditions, modulated by small-scale sea-level oscillations (≈1-2 m) of fith to sixth order. This study also highlights the advantage of an integrated analysis using acoustic/seismic methods for practical assessment of the anthropogenic effects on infralittoral domains based on the association of marine geological observations.

PROM-OPEN: PROMOTING OPEN SCIENCE IN AN ON-LINE E-LEARNING ENVIRONMENT

Peer-reviewed

Competition in notch signaling with cis enriches cell fate decisions

Notch signaling is involved in cell fate choices during the embryonic development of Metazoa. Commonly, Notch signaling arises from the binding of the Notch receptor to its ligands in adjacent cells driving cell-to-cell communication. Yet, cell-autonomous control of Notch signaling through both ligand-dependent and ligand-independent mechanisms is known to occur as well. Examples include Notch signaling arising in the absence of ligand binding, and cis-inhibition of Notch signaling by titration of the Notch receptor upon binding to its ligands within a single cell. Increasing experimental evidences support that the binding of the Notch receptor with its ligands within a cell (cis-interactions) can also trigger a cell-autonomous Notch signal (cis-signaling), whose potential effects on cell fate decisions and patterning remain poorly understood. To address this question, herein we mathematically and computationally investigate the cell states arising from the combination of cis-signaling with additional Notch signaling sources, which are either cell-autonomous or involve cell-to-cell communication. Our study shows that cis-signaling can switch from driving cis-activation to effectively perform cis-inhibition and identifies under which conditions this switch occurs. This switch relies on the competition between Notch signaling sources, which share the same receptor but differ in their signaling efficiency. We propose that the role of cis-interactions and their signaling on fine-grained patterning and cell fate decisions is dependent on whether they drive cis-inhibition or cis-activation, which could be controlled during development. Specifically, cis-inhibition and not cis-activation facilitates patterning and enriches it by modulating the ratio of cells in the high-ligand expression state, by enabling additional periodic patterns like stripes and by allowing localized patterning highly sensitive to the precursor state and cell-autonomous bistability. Our study exemplifies the complexity of regulations when multiple signalng sources share the same receptor and provides the tools for their characterization.

A practical guide for the formulation of propositions in the bayesian approach to DNA evidence interpretation in an adversarial environment

The interpretation of complex DNA profiles is facilitated by a Bayesian approach. This approach requires the development of a pair of propositions: one aligned to the prosecution case and one to the defense case. This note explores the issue of proposition setting in an adversarial environment by a series of examples. A set of guidelines generalize how to formulate propositions when there is a single person of interest and when there are multiple individuals of interest. Additional explanations cover how to handle multiple defense propositions, relatives, and the transition from subsource level to activity level propositions. The propositions depend on case information and the allegations of each of the parties. The prosecution proposition is usually known. The authors suggest that a sensible proposition is selected for the defense that is consistent with their stance, if available, and consistent with a realistic defense if their position is not known.

CD8 engineered cytotoxic T cells reprogram melanoma tumor environment.

NlmCategory="UNASSIGNED">Cytotoxic T lymphocytes (CTL) from CD8β-deficient mice have powerful FasL-mediated cytotoxicity and IFNγ responses, but ablated Ca(2+) and NFAT signaling, which can be restored by transduction with CD8β. Upon infection with lymphocytic choriomeningitis virus (LCMV), these cells yielded GP33-specific CTL (CD8βR) that exhibited high FasL/Fas-mediated cytotoxicity, IFNγ CXCL9 and 10 chemokine responses. Transfer of these cells in B16-GP33 tumor bearing mice resulted in (i) massive T cell tumor infiltration, (ii) strong reduction of myeloid-derived suppressor cells (MDSCs), regulatory T cells (Treg) and IL-17-expressing T helper cells, (iii) maturation of tumor-associated antigen-presenting cells and (iv) production of endogenous, B16 melanoma-specific CTL that eradicated the tumor long after the transferred CD8βR CTL perished. Our study demonstrates that the synergistic combination of strong Fas/FasL mediated cytotoxicity, IFNγ and CXCL9 and 10 responses endows adoptively transferred CTL to reprogram the tumor environment and to thus enable the generation of endogenous, tumoricidal immunity.

University teacher competences in a virtual teaching/learning environment : analysis of a teacher training experience

This paper attempts to shed light on the competencies a teacher must have inorder to teach in online university environments. We will relate a teacher trainingexperience, which was designed taking into account the methodological criteriaestablished in line with previous theoretical principles. The main objective of ouranalysis is to identify the achievements and difficulties of a specific formativeexperience, with the ultimate goal of assessing the suitability of this conceptualmethodologicalframework for the design of formative proposals aiming to contribute tothe development of teacher competencies for virtual environments.

A virtual mathematics learning environment for engineering students

Teachers of the course Introduction to Mathematics for Engineers at the UOC, an online distance-learning university, have designed,developed and tested an online studymaterial. It includes basic pre-university mathematics, indications for correct follow-up of this content and recommendations for finding appropriate support and complementarymaterials. Many different resources are used,depending on the characteristics of thecontents: Flash sequences, interactive applets, WIRIS calculators and PDF files.During the last semester, the new study material has been tested with 119 students. The academic results and student satisfaction have allowed us to outline and prioritise future lines of action.