Search

We investigated the forced convective heat loss from a model of a multi-megawatt cavity receiver of a concentrated solar power (CSP) tower system in a high-pressure wind tunnel. Measurements of 5 geometrical configurations of this model as well as measurement uncertainties are reported in this contribution. The experiment covered a Reynolds number range of between 2 · 10 6 and 8 · 10 6 , based on the external dimensions and flow field. In general, the measured values are highly sensitive to the geometrical configuration, the wind velocity, and the wind direction. The results show that the maximum forced convective heat loss for all configurations occurs when the wind blows from frontal directions of between 60 ° and 80 ° relative to the tower symmetry plane. We found that the peak location does not vary for different inclinations, but does vary for different aperture openings. Also, the results show that the direction of the wind causes the forced convective heat loss to vary with a factor of up to 6.1, but at least with a factor of 2.6. Last but not least, our power-law correlation of the dependency of the forced convective heat loss on the Reynolds number matches literature values. [ABSTRACT FROM AUTHOR]

The mechanical properties of bitumen, such as elasticity/Young's modulus, stickiness/adhesion, hardness and energy loss, and sample deformation were acquired quantitatively and simultaneously with the topology at the microscale, discriminating clearly two separate phases within the bitumen. Temperature-dependent measurements revealed detailed and specific data about the changes of these properties with temperature, enabling the development of predictive models for the performance and durability of asphalt. [ABSTRACT FROM AUTHOR]

Because spring water quality from alpine karst aquifers can change very rapidly during event situations, water abstraction management has to be performed in near real-time. Four summer events (2005-2008) at alpine karst springs were investigated in detail in order to evaluate the spectral absorption coefficient at 254nm (SAC254) as a real-time early warning proxy for faecal pollution. For the investigation Low-Earth-Orbit (LEO) Satellite-based data communication between portable hydrometeorological measuring stations and an automated microbiological sampling device was used. The method for event triggered microbial sampling and analyzing was already established and described in a previous paper. Data analysis including on-line event characterisation (i.e. precipitation, discharge, turbidity, SAC254) and comprehensive E. coli determination (n . 800) indicated that SAC254 is a useful early warning proxy. Irrespective of the studied event situations SAC254 always increased 3 to 6 hours earlier than the onset of faecal pollution, featuring different correlation phases. Furthermore, it seems also possible to use SAC254 as a real-time proxy parameter for estimating the extent of faecal pollution after establishing specific spring and event-type calibrations that take into consideration the variability of the occurrence and the transferability of faecal material It should be highlighted that diffuse faecal pollution from wildlife and live stock sources was responsible for spring water contamination at the investigated catchments. In this respect, the SAC254 can also provide useful information to support microbial source tracking efforts where different situations of infiltration have to be investigated. [ABSTRACT FROM AUTHOR]

The present paper deals with the implementation of online data transferred via LEO satellite communication in a flood forecasting system. Although the project is ongoing, it is already recognised that the information chain: "measurement-transmission-forecast-alert" can be shortened, i.e., the flood danger can be more rapidly communicated to the population at risk. This gain is particularly valuable for medium size catchments where the concentration time (basin time of response to rainfall) is short. [ABSTRACT FROM AUTHOR]

Data communication via Low-Earth-Orbit (LEO) Satellites between portable hydrometeorological measuring stations is the backbone of our system. This networking allows automated event sampling with short time increments also for E. coli field analysis. All activities of the course of the event-sampling can be observed on an internet platform based on a Linux-Server. Conventionally taken samples compared with the auto-sampling procedure revealed corresponding results and were in agreement with the ISO 9308-1 reference method. E. coli concentrations were individually corrected by event specific inactivation coefficients (0.10-0.14 day-1), compensating losses due to sample storage at spring temperature in the auto sampler. Two large summer events in 2005/2006 at an important alpine karst spring (LKAS2) were monitored including detailed analysis of E. coli dynamics (n = 271) together with comprehensive hydrological characterisations. High-resolution time series demonstrated a sudden increase of E. coli concentrations in spring water (approximately 2 log10 units) with a specific time delay after the beginning of the event. Statistical analysis suggested the spectral absorption coefficient measured at 254 nm (SAC254) as an early warning surrogate for real time monitoring of faecal input. Together with the LEO-satellite based system it is a helpful tool for early-warning systems in the field of drinking water protection. [ABSTRACT FROM AUTHOR]

Abstract: Our previous studies have demonstrated the essential roles of the transcription factor Sox9 in the commitment of mesenchymal cells to a chondrogenic cell lineage and in overt chondrogenesis during limb bud development. However, it remains unknown if Sox9 induces chondrogenesis in mesenchyme ectopically in vivo as a master regulator of chondrogenesis. In this study, we first generated mutant mice in which Sox9 was misexpressed in the limb bud mesenchyme. The mutant mouse embryos exhibited polydactyly in limb buds in association with ectopic expression of Sox5 and Sox6 although markers for the different axes of limb bud development showed a normal pattern of expression. Misexpression of Sox9 stimulated cell proliferation in limb bud mesenchyme, suggesting that Sox9 has a role in recruiting mesenchymal cells to mesenchymal condensation. Second, despite the facts that misexpression of Sonic hedgehog (Shh) induces polydactyly in a number of mutant mice and Shh-null mutants have severely defective cartilage elements in limb buds, misexpression of Sox9 did not restore limb bud phenotypes in Shh-null mutants. Rather, there was no expression of Sox9 in digit I of Hoxa13Hd mutant embryos, and Sox9 partially rescued hypodactyly in Hoxa13Hd mutant embryos. These results provide evidence that Sox9 induces ectopic chondrogenesis in mesenchymal cells and strongly suggest that its expression may be regulated by Hox genes during limb bud development. [Copyright &y& Elsevier]

The rising incidence of genitourinary (GU) defects among newborns establishes the need and opportunity to focus research efforts on the amelioration of this growing public-health concern. Sadly, our inability to explain the causes of GU defects can be directly attributed to our lack of understanding of GU gene function. Recently, mouse models have been used to provide new insights into the mechanisms that underlie congenital GU malformations. [ABSTRACT FROM AUTHOR]

Low Earth Orbit Satellites (LEOS) provide world-wide ?nomadic? data-communication using low-cost and low-power ?cellular like? equipment. LEOS allow us to also exploit those regions, which up to now were inaccessible by land-based wireless or geostationary (GEO) satellite systems. First, this paper compares satellite systems and summarizes features of the ORBCOMM LEO-system used. In the main part, a detailed report is given on a hydrogeological prototype implementation for remote water-quality monitoring: setup, obtained results, conclusions and further aspects as well as cost comparisons. As a result, LEO satellite data transmission may be a reliable low-cost alternative even to GSM-SMS for low data volume applications.

Adsorption of the protein bovine serum albumin (BSA) on gold has been tested at various concentrations in aqueous solution by dynamic contact-angle analysis (DCA) and quartz-crystal microbalance (QCM) measurements. With the Wilhelmy plate technique advancing and receding contact angles and the corresponding hysteresis were measured and correlated with the hydrophilicity and the homogeneity of the surface. With electrical admittance measurements of a gold-coated piezoelectrical quartz crystal, layer mass and viscoelastic contributions to the resonator's frequency shift during adsorption could be separated. A correlation was found between the adsorbed mass and the homogeneity and hydrophilicity of the adsorbed film. [ABSTRACT FROM AUTHOR]

Provides information on a study on the use of green fluorescent protein (GFP) fusion genes during mouse embryogenesis. Information on GFP; Materials used in the study; Methodology; Results of the study.

Presents a study which utilized partially grooved, long, rectangular grooves on the garnet surface to stabilize minor loop stripes in a Bloch line memory. Experimental details; Results and discussion; Conclusion.

Presents a study which examined the operation of a major line for the third stripe domain structure in a Bloch line memory using a partial garnet grooving structure. Experimental details; Results and discussion; Conclusion.

The homeobox gene (HOXA13) codes for a transcription factor protein that binds to AT-rich DNA sequences and controls expression of genes during embryonic morphogenesis. Here we present the NMR structure of HOXA13 homeodomain (A13DBD) bound to an 11-mer DNA duplex. A13DBD forms a dimer that binds to DNA with a dissociation constant of 7.5 nM. The A13DBD/DNA complex has a molar mass of 35 kDa consistent with two molecules of DNA bound at both ends of the A13DBD dimer. A13DBD contains an N-terminal arm (residues 324 - 329) that binds in the DNA minor groove, and a Cterminal helix (residues 362 - 382) that contacts the ATAA nucleotide sequence in the major groove. The N370 side-chain forms hydrogen bonds with the purine base of A5* (base paired with T5). Side-chain methyl groups of V373 form hydrophobic contacts with the pyrimidine methyl groups of T5, T6* and T7*, responsible for recognition of TAA in the DNA core. I366 makes similar methyl contacts with T3* and T4*. Mutants (I366A, N370A and V373G) all have decreased DNA binding and transcriptional activity. Exposed protein residues (R337, K343, and F344) make intermolecular contacts at the protein dimer interface. The mutation F344A weakens protein dimerization and lowers transcriptional activity by 76%. We conclude that the non-conserved residue, V373 is critical for structurally recognizing TAA in the major groove, and that HOXA13 dimerization is required to activate transcription of target genes. [ABSTRACT FROM AUTHOR]

Abstract: This work is to clarify the underlying mechanisms of burning pulverised coal in a mixture of . The performance of two different burner designs, single central orifice-type (SCO) and single annular orifice-type (SAO), under oxycoal conditions was examined in a down-fired test facility. Based on detailed in-flame measurements, combined with numerical simulations, the main parameters influencing the stability of a pulverised coal swirl flame were investigated. The oxycoal flame was stabilised at the burner quarl by: increasing the O2 concentration above 34vol% without changes to the air-firing burner design and by modifications of the burner geometry thus changing its aerodynamics. The modification of the burner allowed a decrease of the O2 concentrations to 23vol% for SCO burner and to less than 21vol% for SAO burner. Comprehensive measurement data for axial and tangential velocity, flue gas temperature and oxygen concentration for stable oxy-firing at 21vol% O2 is presented. The results reported can be used as a guideline for a development of an industrial swirl burner capable of stable operation in both regimes, namely: air and oxycoal. [Copyright &y& Elsevier]

In the United States, Japan, United Kingdom, and Sweden, birth defects affecting the growth and development of the genitourinary (GU) regions are becoming increasingly prevalent, with incidences ranging as high as 1 in 125 live births. To understand the basis for these malformations, scientists have begun to examine the function of developmental genes in GU tissues. At the forefront of these investigations are studies examining the role of the 5′ HOX proteins during the formation of the GU region. In this report we discuss what is known about HOXA13 and HOXD13 function during GU development, highlighting some of the cellular and molecular mechanisms controlled by these proteins during the GU formation. Finally, the translational benefits of identifying HOX target genes are discussed; first to explain the prevalence of some GU defects as well as a mechanism to facilitate their prevention in the birth population. [ABSTRACT FROM PUBLISHER]

In the tetrapod limb, the digits (fingers or toes) are the elements most subject to morphological diversification in response to functional adaptations. However, despite their functional importance, the mechanisms controlling digit morphology remain poorly understood. Here we have focused on understanding the special morphology of the thumb (digit 1), the acquisition of which was an important adaptation of the human hand. To this end, we have studied the limbs of the Hoxa13 mouse mutant that specifically fail to form digit 1. We show that, consistent with the role of Hoxa13 in Hoxd transcriptional regulation, the expression of Hoxd13 in Hoxa13 mutant limbs does not extend into the presumptive digit 1 territory, which is therefore devoid of distal Hox transcripts, a circumstance that can explain its agenesis. The loss of Hoxd13 expression, exclusively in digit 1 territory, correlates with increased Gli3 repressor activity, a Hoxd negative regulator, resulting from increased Gli3 transcription that, in turn, is due to the release from the negative modulation exerted by Hox13 paralogs on Gli3 regulatory sequences. Our results indicate that Hoxa13 acts hierarchically to initiate the formation of digit 1 by reducing Gli3 transcription and by enabling expansion of the 5'Hoxd second expression phase, thereby establishing anterior-posterior asymmetry in the handplate. Our work uncovers a mutual antagonism between Gli3 and Hox13 paralogs that has important implications for Hox and Gli3 gene regulation in the context of development and evolution. [ABSTRACT FROM AUTHOR]

Gene expression profiling in E 11 mouse embryos identified high expression of the long noncoding RNA (lncRNA), LNCRNA-HIT in the undifferentiated limb mesenchyme, gut, and developing genital tubercle. In the limb mesenchyme, LncRNA-HIT was found to be retained in the nucleus, forming a complex with p100 and CBP. Analysis of the genome-wide distribution of LncRNA-HIT-p100/CBP complexes by ChIRP-seq revealed LncRNA-HIT associated peaks at multiple loci in the murine genome. Ontological analysis of the genes contacted by LncRNA-HIT-p100/CBP complexes indicate a primary role for these loci in chondrogenic differentiation. Functional analysis using siRNA-mediated reductions in LncRNA-HIT or p100 transcripts revealed a significant decrease in expression of many of the LncRNA-HIT-associated loci. LncRNA-HIT siRNA treatments also impacted the ability of the limb mesenchyme to form cartilage, reducing mesenchymal cell condensation and the formation of cartilage nodules. Mechanistically the LncRNA-HIT siRNA treatments impacted pro-chondrogenic gene expression by reducing H3K27ac or p100 activity, confirming that LncRNA-HIT is essential for chondrogenic differentiation in the limb mesenchyme. Taken together, these findings reveal a fundamental epigenetic mechanism functioning during early limb development, using LncRNA-HIT and its associated proteins to promote the expression of multiple genes whose products are necessary for the formation of cartilage. [ABSTRACT FROM AUTHOR]

The long tendons of the limb extend from muscles that reside in the zeugopod (arm/leg) to their skeletal insertions in the autopod (paw). How these connections are established along the length of the limb remains unknown. Here, we show that mouse limb tendons are formed in modular units that combine to form a functional contiguous structure; in muscle-less limbs, tendons develop in the autopod but do not extend into the zeugopod, and in the absence of limb cartilage the zeugopod segments of tendons develop despite the absence of tendons in the autopod. Analyses of cell lineage and proliferation indicate that distinct mechanisms govern the growth of autopod and zeugopod tendon segments. To elucidate the integration of these autopod and zeugopod developmental programs, we re-examined early tendon development. At E12.5, muscles extend across the full length of a very short zeugopod and connect through short anlagen of tendon progenitors at the presumptive wrist to their respective autopod tendon segment, thereby initiating musculoskeletal integration. Zeugopod tendon segments are subsequently generated by proximal elongation of the wrist tendon anlagen, in parallel with skeletal growth, underscoring the dependence of zeugopod tendon development on muscles for tendon anchoring. Moreover, a subset of extensor tendons initially form as fused structures due to initial attachment of their respective wrist tendon anlage to multiple muscles. Subsequent individuation of these tendons depends on muscle activity. These results establish an integrated model for limb tendon development that provides a framework for future analyses of tendon and musculoskeletal phenotypes. [ABSTRACT FROM AUTHOR]

The realisation of a novel concept for automated on-line monitoring of enzymatic activities in water was successfully demonstrated by long-term field testing at two remote Austrian ground water resources. The β-D-glucuronidase (GLUC) activity was selected as a representative enzymatic model parameter for the on-line determination. But the device can be adapted for any enzymatic reaction with diagnostic relevance for microbial water quality monitoring, as demonstrated for the β-Dgalactosidase activity. Automated filtration of volumes up to 5 litres supports sensitive quantification of enzymatic activities. Internet-based data transfer, using internal control parameters for verification and a dynamic determination of the limit of quantification, enabled robust enzymatic on-line monitoring during a 2-year period. A proportion of 5,313 out of 5,506 GLUC activity measurements (96.5%) could be positively verified. Hydrological (discharge, gauge, turbidity, temperature, pH, electric conductivity, spectral absorbance coefficient at 254 nm) as well as microbiological parameters (Escherichia coli, coliforms) were concurrently determined to characterise the investigated ground water resources. The enzymatic on-line measurements closely reflected the different hydrological conditions and contamination patterns of the test sites. Contrary to expectations, GLUC did not qualify as a proxy-parameter for the occurrence of cultivation-based E. coli contamination and warrants further detailed investigations on its indication capacity as a rapid means for microbial faecal pollution detection in such aquatic habitats. Microbial on-line monitoring is likely to become more important in the future, complementing existing surveillance strategies for water safety management. Further perspectives on the application of such analytical on-line technologies, such as their connection with event-triggered sampling and standardised diagnostics, are discussed. [ABSTRACT FROM AUTHOR]

Water resource management must strive to link catchment information with water quality monitoring. The present study attempted this for the field of microbial fecal source tracking (MST). A fecal pollution source profile based on catchment data (e.g., prevalence of fecal sources) was used to formulate a hypothesis about the dominant sources of pollution in an Austrian mountainous karst spring catchment. This allowed a statistical definition of methodical requirements necessary for an informed choice of MST methods. The hypothesis was tested in a 17-month investigation of spring water quality. The study followed a nested sampling design in order to cover the hydrologicai and pollution dynamics of the spring and to assess effects such as differential persistence between parameters. Genetic markers for the potential fecal sources as well as microbiological, hydrological, and chemo-physical parameters were measured. The hypothesis that ruminant animals were the dominant sources of fecal pollution in the catchment was clearly confirmed. It was also shown that the concentration of ruminant markers in feces was equally distributed in different ruminant source groups. The developed approach provides a tool for careful decision-making in MST study design and might be applied on various types of catchments and pollution situations. [ABSTRACT FROM AUTHOR]

Abstract: Oxyfuel processes represent a promising technique for carbon capture and storage since the related energy penalty is considered to be comparatively low. A possibility to separate the O2 from air is the use of mixed ion electron conducting (MIEC) membranes. A favored membrane material is Ba0.5Sr0.5Co0.8Fe0.2O3−δ since its permeation rate is high. In the work at hand this membrane material has been studied experimentally to determine the coefficients of the Wagner equation. The experiments have been performed with membrane tubes considering the use of tubular membrane systems for industrial application in future oxyfuel power plants. 3- and 4-end operating conditions have been applied to provide an additional degree of freedom for the integration of the membrane module into the power plant process. Wagner constants C = mol/(cmsK) and K =6201K have been determined. A membrane model for Aspen Plus has been developed, which allows to calculate the heat and mass transfer in an oxygen membrane module. Calculations were performed based on data from oxyfuel membrane power plant simulations found in the literature. Compared to the 3-end concept the 4-end concept shows a higher net-efficiency together with a lower demand on membrane area. Depending on the operation mode and boundary conditions, the estimated specific membrane area is between 0.22 and 0.59 /. [Copyright &y& Elsevier]

Abstract: We report on the pattern formation in the thin film of the Ni+C60 mixture deposited on the MgO(001) substrate at room temperature (RT). Using magnetic force microscopy a periodic array of the magnetic domains has been revealed. The domains reflect hidden partitioning of the Ni+C60 film (i.e., separated Ni- and C60-rich zones) that has not been observed by other applied methods. The effect indicates that even at RT, spontaneous separation of the Ni and C60 phases may set in during the growth of the hybrid film. Thermal annealing (for 1h at 500°C) leads to dramatic rearrangement of the Ni+C60 structure which (consequently) also results in the loss of the magnetic domain system. This phenomenon points out the thermodynamic instability of the as-prepared hybrid film that can (at elevated temperatures) trigger the process of the Ni and C60 phase separation. [Copyright &y& Elsevier]

Abstract: A novel approach to oxycoal flame stabilization has been developed at the Institute of Heat and Mass Transfer at RWTH Aachen University [D. Toporov, M. Förster, R. Kneer, in: Third Int. Conf. on Clean Coal Technologies for Our Future, Cagliari, Sardinia, Italy, 15–17 May 2007]. The swirl burner design and its operating conditions have been adjusted in order to enforce CO formation thus stabilizing the flame and obtaining a full burnout at levels of O2 content in the O2/CO2 mixture similar to those in air. The paper presents results of detailed numerical and experimental investigations of a stable oxy-fired pulverized coal swirl flame (type-2) obtained with a 21 vol% O2 concentration. The combustion tests were performed in a vertical pilot-scale furnace (100 kWth) in the framework of the OXYCOAL-AC research project aiming to develop a membrane-based oxyfuel process. The experimental results concerning gas velocities, gas and particle temperatures, and gas compositions are presented and discussed, focusing on the underlying mechanisms as well as on the aerodynamics of the oxycoal flame. A comparison between measurements and simulations has shown the validity of the numerical method used. The reported data set can be used for validation of numerical models developed for prediction of oxyfuel combustion. [Copyright &y& Elsevier]

The impairment of water quality by faecal pollution is a global public health concern. Microbial source tracking methods help to identify faecal sources but the few recent quantitative microbial source tracking applications disregarded catchment hydrology and pollution dynamics. This quantitative microbial source tracking study, conducted in a large karstic spring catchment potentially influenced by humans and ruminant animals, was based on a tiered sampling approach: a 31-month water quality monitoring (Monitoring) covering seasonal hydrological dynamics and an investigation of flood events (Events) as periods of the strongest pollution. The detection of a ruminant-specific and a human-specific faecal Bacteroidetes marker by quantitative real-time PCR was complemented by standard microbiological and on-line hydrological parameters. Both quantitative microbial source tracking markers were detected in spring water during Monitoring and Events, with preponderance of the ruminant-specific marker. Applying multiparametric analysis of all data allowed linking the ruminant-specific marker to general faecal pollution indicators, especially during Events. Up to 80% of the variation of faecal indicator levels during Events could be explained by ruminant-specific marker levels proving the dominance of ruminant faecal sources in the catchment. Furthermore, soil was ruled out as a source of quantitative microbial source tracking markers. This study demonstrates the applicability of quantitative microbial source tracking methods and highlights the prerequisite of considering hydrological catchment dynamics in source tracking study design. [ABSTRACT FROM AUTHOR]

In eutherian mammals, embryonic growth and survival is dependent on the formation of the placenta, an organ that facilitates the efficient exchange of oxygen, nutrients, and metabolic waste between the maternal and fetal blood supplies. Key to the placenta's function is the formation of its vascular labyrinth, a series of finely branched vessels whose molecular ontogeny remains largely undefined. In this report, we demonstrate that HOXA13 plays an essential role in labyrinth vessel formation. In the absence of HOXA13 function, placental endothelial cell morphology is altered, causing a loss in vessel wall integrity, edema of the embryonic blood vessels, and mid-gestational lethality. Microarray analysis of wild-type and mutant placentas revealed significant changes in endothelial gene expression profiles. Notably, pro-vascular genes, including Tie2 and Foxf1, exhibited reduced expression in the mutant endothelia, which also exhibited elevated expression of genes normally expressed in lymphatic or sinusoidal endothelia. ChIP analysis of HOXA13–DNA complexes in the placenta confirmed that HOXA13 binds the Tie2 and Foxf1 promoters in vivo. In vitro, HOXA13 binds sequences present in the Tie2 and Foxf1 promoters with high affinity (Kd = 27–42 nM) and HOXA13 can use these bound promoter regions to direct gene expression. Taken together, these findings demonstrate that HOXA13 directly regulates Tie2 and Foxf1 in the placental labyrinth endothelia, providing a functional explanation for the mid-gestational lethality exhibited by Hoxa13 mutant embryos as well as a novel transcriptional program necessary for the specification of the labyrinth vascular endothelia. [ABSTRACT FROM AUTHOR]

Mutations in Hoxa13 cause malformations of the appendicular skeleton and genitourinary tract, including digit loss, syndactyly, and hypospadias. To determine the molecular basis for these defects, the DNA sequences bound by HOXA13 were empirically determined, revealing a novel high affinity binding site. Correlating the utilization of this high affinity binding site with genes exhibiting perturbed expression in Hoxa13 mutant limbs, we identified that HOXA13 suppresses the expression of the BMP antagonist, Sostdc1. In the absence of HOXA13 function, Sostdc1 is ectopically expressed in the distal limb, causing reduced expression of BMP-activated genes and decreased SMAD phosphorylation. Limb chromatin immunoprecipitation revealed HOXA13 binding at its high affinity site in two conserved Sostdc1 regulatory sites in vivo. In vitro, HOXA13 represses gene expression through the Sostdc1 high affinity binding sites in a dosage-dependent manner. Together, these findings confirm that the high affinity HOXA13 binding site deduced by quantitative analyses is used in vivo to facilitate HOXA13 target gene regulation, providing a critical advance toward understanding the molecular basis for defects associated with the loss of HOXA13 function. [ABSTRACT FROM AUTHOR]

In humans and mice, loss of HOXA13 function causes defects in the growth and patterning of the digits and interdigital tissues. Analysis of Hoxa13 expression reveals a pattern of localization overlapping with sites of reduced Bmp2 and Bmp7 expression in Hoxa13 mutant limbs. Biochemical analyses identified a novel series of Bmp2 and Bmp7 enhancer regions that directly interact with the HOXA13 DNA-binding domain and activate gene expression in the presence of HOXA13. Immunoprecipitation of HOXA13-Bmp2 and HOXA13-Bmp7 enhancer complexes from the developing autopod confirm that endogenous HOXA13 associates with these regions. Exogenous application of BMP2 or BMP7 partially rescues the Hoxa13 mutant limb phenotype, suggesting that decreased BMP signaling contributes to the malformations present in these tissues. Together, these results provide conclusive evidence that HOXA13 regulates Bmp2 and Bmp7 expression, providing a mechanistic link between HOXA13, its target genes and the specific developmental processes affected by loss of HOXA13 function. [ABSTRACT FROM AUTHOR]

Presents information on a study which evaluated evidence that hypospadia in mice lacking Hoxa13 is caused by defects in UPE maturation, signaling and proliferative induction of the surrounding genital tubercle (GT) mesenchyme. Exhibition of reduced mitosis by Hoxa13-deficient in the GT; Analysis of the mechanisms underlying reduced programmed cell death in the mutant GT; Effects of perturbations in Bmp signaling.

In most tetrapod vertebrates, limb skeletal progenitors condense with postaxial dominance. Posterior elements (such as ulna and fibula) appear prior to their anterior counterparts (radius and tibia), followed by digit-appearance order with continuing postaxial polarity. The only exceptions are urodele amphibians (salamanders), whose limb elements develop with preaxial polarity and who are also notable for their unique ability to regenerate complete limbs as adults. The mechanistic basis for this preaxial dominance has remained an enigma and has even been proposed to relate to the acquisition of novel genes involved in regeneration. However, recent fossil evidence suggests that preaxial polarity represents an ancestral rather than derived state. Here, we report that 5′ Hoxd (Hoxd11-d13) gene deletion in mouse is atavistic and uncovers an underlying preaxial polarity in mammalian limb formation. We demonstrate this shift from postaxial to preaxial dominance in mouse results from excess Gli3 repressor (Gli3R) activity due to the loss of 5′Hoxd-Gli3 antagonism and is associated with cell-cycle changes promoting precocious cell-cycle exit in the anterior limb bud. We further show that Gli3 knockdown in axolotl results in a shift to postaxial dominant limb skeleton formation, as well as expanded paddle-shaped limb-bud morphology and ensuing polydactyly. Evolutionary changes in Gli3R activity level, which also played a key role in the fin-to-limb transition, appear to be fundamental to the shift from preaxial to postaxial polarity in formation of the tetrapod limb skeleton. [Display omitted] • Gli3 repressor (Gli3R) activity level governs tetrapod limb axis formation polarity • 5′Hoxd-Gli3 balance modulates cell-cycle exit to determine mouse limb axis polarity • Alternating A-P digit appearance in mammals is linked to primary limb axis polarity • Axolotl Gli3 knockdown shifts the ancestral preaxial dominance to postaxial Uniquely in salamanders, the tetrapod primary limb axis forms with ancestral preaxial dominance, but the underlying basis is unknown. Here, Trofka et al. show Gli3 has a central role; mice with elevated Gli3 repressor activity revert to preaxial dominance. Conversely, Gli3 knockdown shifts the axolotl limb axis from preaxial to postaxial polarity. [ABSTRACT FROM AUTHOR]

Reciprocal epithelial-mesenchymal interactions shape site-specific development of skin. Here we show that site-specific HOX expression in fibroblasts is cell-autonomous and epigenetically maintained. The distal-specific gene HOXA13 is continually required to maintain the distal-specific transcriptional program in adult fibroblasts, including expression of WNT5A, a morphogen required for distal development. The ability of distal fibroblasts to induce epidermal keratin 9, a distal-specific gene, is abrogated by depletion of HOXA13, but rescued by addition of WNT5A. Thus, maintenance of appropriate HOX transcriptional program in adult fibroblasts may serve as a source of positional memory to differentially pattern the epithelia during homeostasis and regeneration. [ABSTRACT FROM AUTHOR]