Loss-of-function mutations of an inhibitory upstream ORF in the human hairless transcript cause Marie Unna hereditary hypotrichosis.

Marie Unna hereditary hypotrichosis (MUHH) is an autosomal dominant form of genetic hair loss. In a large Chinese family carrying MUHH, we identified a pathogenic initiation codon mutation in U2HR, an inhibitory upstream ORF in the 5' UTR of the gene encoding the human hairless homolog (HR). U2HR is predicted to encode a 34-amino acid peptide that is highly conserved among mammals. In 18 more families from different ancestral groups, we identified a range of defects in U2HR, including loss of initiation, delayed termination codon and nonsense and missense mutations. Functional analysis showed that these classes of mutations all resulted in increased translation of the main HR physiological ORF. Our results establish the link between MUHH and U2HR, show that fine-tuning of HR protein levels is important in control of hair growth, and identify a potential mechanism for preventing hair loss or promoting hair removal.

Physical quality of an Oxisol cultivated with maize submited to cover crops in the pre-cropping period

The intensive use of land alters the distribution of the pore size which imparts consequences on the soil physical quality. The Least Limiting Water Range (LLWR) allows for the visualization of the effects of management systems upon either the improvement or the degradation of the soil physical quality. The objective of this study was to evaluate the physical quality of a Red Latosol (Oxisol) submited to cover crops in the period prior to the maize crop in a no-tillage and conventional tillage system, using porosity, soil bulk density and the LLWR as attributes. The treatments were: conventional tillage (CT) and a no-tillage system with the following cover crops: sunn hemp (Crotalaria juncea L.) (NS), pearl millet (Pennisetum americanum (L.) Leeke) (NP) and lablab (Dolichos lablab L.) (NL). The experimental design was randomized blocks in subdivided plots with six replications, with the plots being constituted by the treatments and the subplots by the layers analyzed. The no-tillage systems showed higher total porosity and soil organic matter at the 0-0.5 m layer for the CT. The CT did not differ from the NL or NS in relation to macroporosity. The NP showed the greater porosity, while CT and NS presented lower soil bulk density. No < 10 % airing porosity was found for the treatments evaluated, and value for water content where soil aeration is critical (θPA) was found above estimated water content at field capacity (θFC) for all densities. Critical soil bulk density was of 1.36 and 1.43 Mg m-3 for NP and CT, respectively. The LLWR in the no-tillage systems was limited in the upper part by the θFC, and in the bottom part, by the water content from which soil resistance to penetration is limiting (θPR). By means of LLWR it was observed that the soil presented good physical quality.

Spatial variability of physical attributes of an alfisol under different hillslope curvatures

The influence of relief forms has been studied by several authors and explains the variability in the soil attributes of a landscape. Soil physical attributes depend on relief forms, and their assessment is important in mechanized agricultural systems, such as of sugarcane. This study aimed to characterize the spatial variability in the physical soil attributes and their relationship to the hillslope curvatures in an Alfisol developed from sandstone and growing sugarcane. Grids of 100 x 100 m were delimited in a convex and a concave area. The grids had a regular spacing of 10 x 10 m, and the crossing points of this spacing determined a total of 121 georeferenced sampling points. Samples were collected to determine the physical attributes related to soil aggregates, porosity, bulk density, resistance to penetration and moisture within the 0-0.2 and 0.2-0.4 m depth. Statistical analyses, geostatistics and Student's t-tests were performed with the means of the areas. All attributes, except aggregates > 2 mm in the 0-0.2 m depth and macroporosity at both depths, showed significant differences between the hillslope curvatures. The convex area showed the highest values of the mean weighted diameter, mean geometric diameter, aggregates > 2 mm, 1-2 mm aggregates, total porosity and moisture and lower values of bulk density and resistance to penetration in both depth compared to the concave area. The number of soil attributes with greater spatial variability was higher in the concave area.

Comparison between molecular dynamics abd Monte Carlo simulations of an ordering process in a binary alloy

Ordering in a binary alloy is studied by means of a molecular-dynamics (MD) algorithm which allows to reach the domain growth regime. Results are compared with Monte Carlo simulations using a realistic vacancy-atom (MC-VA) mechanism. At low temperatures fast growth with a dynamical exponent x>1/2 is found for MD and MC-VA. The study of a nonequilibrium ordering process with the two methods shows the importance of the nonhomogeneity of the excitations in the system for determining its macroscopic kinetics.

Nitrogen fertilizer use efficiency, recovery and leaching of an alexandergrass pasture

Nitrogen usually determines the productive potential of forage crops, although it is highly unstable in the environment. Studies on recovery rates and use efficiency are important for more reliable fertilizer recommendations to reduce costs and avoid environmental pollution. The purpose of this study was to evaluate N use efficiency and recovery rate of Alexandergrass pasture (Brachiaria - Syn. Urochloa plantaginea) as well as N-NO3- and N-NH4+ soil concentrations using different levels of N fertilization under two grazing intensities. The experiment was arranged in a randomized block design in a factorial scheme with three replications. Treatments consisted of three N rates (0, 200 and 400 kg ha-1 N) and two grazing intensities termed low mass (LM; forage mass of 2,000 kg ha-1 of DM) and high mass (HM; forage mass of 3,600 kg ha-1 of DM) under continuous stocking and variable stocking rates. Results of N fertilization with 200 kg ha-1 were better than with 400 kg ha-1 N. There was a significant effect of N rates on soil N-NO3-concentration with higher levels in the first layer of the soil profile in the treatment with 400 kg ha-1 N. Grazing intensity also affected soil N-NO3- concentration, by increasing the levels under the higher stocking rate (lower forage mass).

Decay of an unstable state in the presence of multiplicative noise

The phenomenon of anomalous fluctuations associated with the decay of an unstable state is analyzed in the presence of multiplicative noise. A theory is presented and compared with a numerical simulation. Our results allow us to distinguish the roles of additive and multiplicative noise in the nonlinear relaxation process. We suggest the use of experiments on transient dynamics to understand the effect of these two sources of noise in problems in which parametric noise is thought to be important, such as dye lasers.

Development of an Fn14 agonistic antibody as an anti-tumor agent.

TWEAK, a TNF family ligand with pleiotropic cellular functions, was originally described as capable of inducing tumor cell death in vitro. TWEAK functions by binding its receptor, Fn14, which is up-regulated on many human solid tumors. Herein, we show that intratumoral administration of TWEAK, delivered either by an adenoviral vector or in an immunoglobulin Fc-fusion form, results in significant inhibition of tumor growth in a breast xenograft model. To exploit the TWEAK-Fn14 pathway as a therapeutic target in oncology, we developed an anti-Fn14 agonistic antibody, BIIB036. Studies described herein show that BIIB036 binds specifically to Fn14 but not other members of the TNF receptor family, induces Fn14 signaling, and promotes tumor cell apoptosis in vitro. In vivo, BIIB036 effectively inhibits growth of tumors in multiple xenograft models, including colon (WiDr), breast (MDA-MB-231), and gastric (NCI-N87) tumors, regardless of tumor cell growth inhibition response observed to BIIB036 in vitro. The anti-tumor activity in these cell lines is not TNF-dependent. Increasing the antigen-binding valency of BIB036 significantly enhances its anti-tumor effect, suggesting the contribution of higher order cross-linking of the Fn14 receptor. Full Fc effector function is required for maximal activity of BIIB036 in vivo, likely due to the cross-linking effect and/or ADCC mediated tumor killing activity. Taken together, the anti-tumor properties of BIIB036 validate Fn14 as a promising target in oncology and demonstrate its potential therapeutic utility in multiple solid tumor indications.

Chemical and microbiological attributes of an oxisol treated with successive applications of sewage sludge¹

Studies on sewage sludge (SS) have confirmed the possibilities of using this waste as fertilizer and/or soil conditioner in crop production areas. Despite restrictions with regard to the levels of potentially toxic elements (PTE) and pathogens, it is believed that properly treated SS with low PTE levels, applied to soil at adequate rates, may improve the soil chemical and microbiological properties. This study consisted of a long-term field experiment conducted on a Typic Haplorthox (eutroferric Red Latosol) treated with SS for seven successive years for maize production, to evaluate changes in the soil chemical and microbiological properties. The treatments consisted of two SS rates (single and double dose of the crop N requirement) and a mineral fertilizer treatment. Soil was sampled in the 0-0.20 m layer and analyzed for chemical properties (organic C, pH, P, K, Ca, Mg, CEC, B, Cu, Fe, Mn, Zn, Cd, Ni, and Pb) and microbiological properties (basal respiration, microbial biomass activity, microbial biomass C, metabolic quotient, microbial quotient, and protease and dehydrogenase enzyme activities). Successive SS applications to soil increased the macro- and micronutrient availability, but the highest SS dose reduced the soil pH significantly, indicating a need for periodic corrections. The SS treatments also affected soil microbial activity and biomass negatively. There were no significant differences among treatments for maize grain yield. After seven annual applications of the recommended sludge rate, the heavy metal levels in the soil had not reached toxic levels.

Passage times for the decay of an unstable state triggered by colored noise

We study the decay of an unstable state in the presence of colored noise by calculating the moment generating function of the passage-time distribution. The problems of the independence of the initial condition in this non-Markovian process and that of nonlinear effects are addressed. Our results are compared with recent analog simulations.

Influence of organic-mineral fertilization of an oxisol on soil chemical properties and Bracharia brizantha production

The use of organic-mineral fertilizer produced by the manufacturing industry of lysine and threonine amino acids can improve the fertility of tropical soils. The objective of this study was to evaluate the influence of different doses of the organic-mineral fertilizer named Ajifer L-14 on chemical properties and on the response with increased production of a forage on a Red Latosol in the northwestern region of São Paulo State, Brazil. A randomized block design was used with seven treatments and four replications. The treatments consisted of: T1- control (without application of Ajifer L-14); T2- control (natural vegetation); T3- mineral fertilization according to crop requirements and soil analysis (application of 1.35 kg plot-1 of urea, 2.20 single superphosphate, and 0.51 KCl, corresponding to 60 of N, 40 P2O5 and 30 kg ha-1 of K2O); T4- fertilization with Ajifer L-14 according to the recommendation resulting from the soil chemical analysis (40 L plot-1, corresponding to 60 kg ha-1 N); T5- fertilization with Ajifer L-14, at a rate of 150 % of the recommended values (60 L plot-1, corresponding to 90 kg ha-1 N); T6- fertilization with Ajifer L-14 at a rate of 50 % of the recommended values (20 L plot-1, corresponding to 30 kg ha-1 N); T7- fertilization with Ajifer L-14 at a rate of 125 % of the recommended values (50 L plot-1, corresponding to 75 kg ha-1 N); T8- fertilization with Ajifer L-14 at a rate of 75 % of the recommended values (30 L plot-1, corresponding to 45 kg ha-1 N). The following soil chemical properties were evaluated (layers 0.0-0.1 and 0.1-0.2 m): P, organic matter, pH, K+, Ca2+, Mg2+, cation exchange capacity, potential acidity, and base saturation. The application of this organic-mineral fertilizer does not influence the soil chemical properties. Regression analysis indicated a polynomial relationship between the application rates of organic-mineral fertilizer and the production of dry matter and crude protein of Bracharia Brizantha.

Physical properties of an Alfisol and no-till soybean yield

It is known that any kind of soil management causes changes in the soil physical characteristics and can affect agricultural yield. The purpose of this study was to evaluate soil properties of an Alfisol and soybean yield under different management systems for no-tillage annual crops, no-tillage with chiseling and no-tillage crop rotation. The 11-year experiment was initiated in the 1998/99 growing season, on 100 x 30 m plots (11 % slope). Soil samples (5 per management system) were systematically collected (0-25 cm layer) in the summer growing season, to quantify soil organic matter, bulk density, macroporosity and flocculation, as well as soybean yield. The highest values for soil bulk density and organic matter content and the lowest for macroporosity were observed in the no-till system alone, whereas in the no-till system with quarterly chiseling the values for organic matter content were lowest, and no-tillage crop rotation resulted in the highest values for organic matter and macroporosity, and the lowest for soil bulk density. The average soybean yield was highest under no-till and trimestrial chiseling or crop rotation, and lowest for no-tillage annual crops no-tillage annual crops alone.

Expansion and tissue infiltration of an allospecific CD4+CD25+CD45RO+IL-7Ralphahigh cell population in solid organ transplant recipients.

It has been recently shown (Seddiki, N., B. Santner-Nanan, J. Martinson, J. Zaunders, S. Sasson, A. Landay, M. Solomon, W. Selby, S.I. Alexander, R. Nanan, et al. 2006. J. Exp. Med. 203:1693-1700.) that the expression of interleukin (IL) 7 receptor (R) alpha discriminates between two distinct CD4 T cell populations, both characterized by the expression of CD25, i.e. CD4 regulatory T (T reg) cells and activated CD4 T cells. T reg cells express low levels of IL-7Ralpha, whereas activated CD4 T cells are characterized by the expression of IL-7Ralpha(high). We have investigated the distribution of these two CD4 T cell populations in 36 subjects after liver and kidney transplantation and in 45 healthy subjects. According to a previous study (Demirkiran, A., A. Kok, J. Kwekkeboom, H.J. Metselaar, H.W. Tilanus, and L.J. van der Laan. 2005. Transplant. Proc. 37:1194-1196.), we observed that the T reg CD25(+)CD45RO(+)IL-7Ralpha(low) cell population was reduced in transplant recipients (P < 0.00001). Interestingly, the CD4(+)CD25(+)CD45RO(+)IL-7Ralpha(high) cell population was significantly increased in stable transplant recipients compared with healthy subjects (P < 0.00001), and the expansion of this cell population was even greater in patients with documented humoral chronic rejection compared with stable transplant recipients (P < 0.0001). The expanded CD4(+)CD25(+)CD45RO(+)IL-7Ralpha(high) cell population contained allospecific CD4 T cells and secreted effector cytokines such as tumor necrosis factor alpha and interferon gamma, thus potentially contributing to the mechanisms of chronic rejection. More importantly, CD4(+)IL-7Ralpha(+)and CD25(+)IL-7Ralpha(+) cells were part of the T cell population infiltrating the allograft of patients with a documented diagnosis of chronic humoral rejection. These results indicate that the CD4(+)CD25(+)IL-7Ralpha(+) cell population may represent a valuable, sensitive, and specific marker to monitor allospecific CD4 T cell responses both in blood and in tissues after organ transplantation.

Landau damping of transverse quadrupole oscillations of an elongated Bose-Einstein condensate

We have studied the interaction between the low-lying transverse collective oscillations and the thermal excitations of an elongated Bose-Einstein condensate by means of perturbation theory. We consider a cylindrical trapped condensate and calculate the transverse elementary excitations at zero temperature by solving the linearized Gross-Pitaevskii equations in two dimensions (2D). We use them to calculate the matrix elements between the thermal excited states and the quasi-2D collective modes. The Landau damping of transverse collective modes is studied as a function of temperature. At low temperatures, the corresponding damping rate is in agreement with the experimental data for the decay of the transverse quadrupole mode, but it is too small to explain the observed slow decay of the transverse breathing mode. The reason for this discrepancy is discussed.

Biocompatibility of an x-shaped zirconium implant in deep sclerectomy in rabbits

ABSTRACT : Background : The aim of this study was to evaluate the midterm biocompatibility of a new x-shaped implant made of zirconium in an animal model of glaucoma surgery. Methods : Preoperatively, ultrasound biomicroscopy (UBM), intraocular pressure (IOP) and outflow facility (OF) data were acquired. Upon surgery, one eye was chosen randomly to receive an implant, while the other received none. Ten rabbits went through a 1-, 2-, 3-, 4- and 6-month follow-up. [OP was measured regularly, UBM performed at 1, 3 and 6 months after surgery. At the end of the follow-up, OF was again measured. Histology sections were analyzed. Results : For both groups IOP control was satisfactory, while OF initially increased at month 1 to resume preoperative values thereafter. Eyes with implants had larger filtration blebs which decreased faster than in eyes without the implant. Drainage vessel density, inflammatory cell number and fibrosis were higher in tissues near the implant. Conclusions : The zirconium implant initially promoted the positive effects of the surgery (IOP control, OF increase). Nevertheless, after several months, foreign body reactions and fibrosis had occurred on some implants that restrained the early benefit of such a procedure. Modifications of the zirconium implant geometry could enhance the overall success rate.