Position-independent expression of a human nerve growth factor-luciferase reporter gene cloned on a yeast artificial chromosome vector.

Two yeast artificial chromosomes containing the entire human nerve growth factor gene were isolated and mapped. By homologous recombination a luciferase gene was precisely engineered into the coding portion of the NGF gene and a neomycin selection marker was placed adjacent to one of the YAC telomeres. Expression of the YAC-based NGF reporter gene and a plasmid-based NGF reporter gene were compared with the regulation of endogenous mouse NGF protein in mouse L929 fibroblasts. In contrast to the plasmid-based reporter gene, expression and regulation of the YAC-based reporter gene was independent of the site of integration of the transgene. Basic fibroblast growth factor and okadaic acid stimulated expression of the YAC transgene, whereas transforming growth factor-beta and dexamethasone inhibited it. Although cyclic AMP strongly stimulated production of the endogenous mouse NGF, no effect was seen on the human NGF reporter genes. Downregulation of the secretion of endogenous mouse NGF already occurred at an EC50 of 1-2 nM dexamethasone, but downregulation of the expression of NGF reporter genes occurred only at EC50 of 10 nM. This higher concentration was also required for upregulation of luciferase genes driven by the dexamethasone-inducible promoter of the mouse mammary tumor virus in L929 fibroblasts.     

A new synthetic route towards heterotrimetallic complexes. Synthesis, crystal structure and magnetic properties of a [CuMnCr] trinuclear complex

The heterotrimetallic complex, [{LCuMn(H₂O)}{Cr(phen)(C₂O₄)₂}](ClO₄) · H₂O (1), has been obtained by assembling heterobinuclear cations, [LCuMn]²⁺, with [Cr(phen)(C₂O₄)₂]⁻ ions (H₂L is the compartmental Schiff-base resulting from the stepwise condensation of 2,6-diformyl-p-cresol with ethylenediamine and diethylenetriamine). The copper(II) and manganese(II) ions are hosted into the compartments of the macrocyclic ligand. [Cr(phen)(C₂O₄)₂]⁻ acts as a ligand, being coordinated through one oxalato oxygen atom to the apical position of the square pyramidal copper(II) ion. The cryomagnetic investigation of 1 reveals an antiferromagnetic interaction between Cu^II and Mn^II within the compartmental ligand (J = −39 cm⁻¹). The interaction between Cu^II and Cr^III across the oxalato bridge is negligible. The crystal structure of [LCuPb](ClO₄)₂ · H₂O, a useful precursor in obtaining 3d-3d′ complexes, is also reported.     

Inequality in Japan (1892–1941): Physical stature, income, and health

This paper investigates the relationship between physical stature, per capita income, health, and regional inequality in Japan at the prefecture-level for the period 1892-1941. The analysis shows that inequality in income and access to health services explains differences in average height of the population across the 47 Japanese prefectures during this period and that variation in income contributed to changes in height during the 1930s. Annual regional time series of height indicate that Japan experienced a regional convergence in biological welfare before 1914, and that a divergence occurred during the interwar period; personal inequality followed a similar pattern.     

Inflammatory demyelinating neuropathies: classification, evolution and prognosis

Inflammatory demyelinating neuropathies can be classified according to the topography of the nervous lesion. Acute and chronic polyradiculoneuritis are characterized by diffuse and multifocal, but predominantly proximal lesions, multifocal motor and sensory-motor neuropathies with persistent conduction blocks are restricted to some nerve trunks, while neuropathies due to monoclonal IgM with anti-MAG (Myelin Associated Glycoprotein) activity show distal and symmetric distribution. The clinical characteristics of inflammatory demyelinating neuropathies vary according to the type of neuropathy. Their course can be remittent or progressive but is especially marked by the risk of definitive axonal lesions, source of permanent neurological deficits. These neuropathies correspond to various mechanisms, which can be differentiated according to the antigenic target, the type of immunological disorder (with respect to cellular or humoral predominance), and the adapted therapeutic strategy. The inflammatory process is accompanied by energetic failure, leading to Na+/K+ pump impairment and intra-axonal Na+ accumulation. This failure results in Na+/Ca2+ exchanger activation, provoking neuronal Ca2+ influx, enzymatic proteolysis and axonal degeneration.     

Why preen others? Predictors of allopreening in parrots and corvids and comparisons to grooming in great apes

Allogrooming in primates serves not only a hygienic function, but also plays a crucial role in maintaining strong affiliative bonds between group members, which in turn, underpin the emergence of cooperative behavior. In contrast, although allopreening occurs in many avian species, we know little about its social functions. Our study addresses this issue by investigating allopreening in a broad comparative data set including six corvid and nine parrot species. We assessed whether rates of allopreening initiations, proportion of time spent allopreening, and the number of grooming partners in captive group-housed birds were comparable to patterns observed in captive chimpanzees and bonobos. While parrots and corvids were found to have similar rates of social grooming to bonobos and chimpanzees, Pan species dedicated significantly more time to social grooming. Animals in larger groups had more grooming partners, but when controlling for the number of potential partners, birds tended to have fewer grooming interaction partners than Pan species. We then investigated whether allopreening in parrots and corvids was predicted by behavioral markers of affiliative social bonds (close physical proximity, active feeding, and low levels of agonistic behavior). Results revealed that providing allopreening to a partner was significantly predicted by often being in close proximity, but not engagement in active feeding or agonistic behavior. We examined the region allopreened in a subset of species and found that preening a partner's head was predicted by both close physical proximity and active feeding, while body allopreening was only predicted by close physical proximity. Head preening may confer more hygienic benefits to recipients, and thus, may be more selectively provided to valued partners. Results support the hypothesis that allopreening in corvids and parrots helps maintain social bonds with an individual's most important social partners, showing some similarities to allogrooming in primates.     

SSR182289A, a selective and potent orally active thrombin inhibitor

SSR182289A 1 is the result of a rational optimisation process leading to an orally active thrombin inhibitor. The structure incorporates an original 2-(acetylamino)-[1,1'-biphenyl]-3-sulfonyl N-terminal motif, a central l-Arg surrogate carrying a weakly basic 3-amino-pyridine, and an unusual 4-difluoropiperidine at the C-terminus. Its synthesis is convergent and palladium catalysis has been employed for the construction of the key C-C bonds: Suzuki coupling for the bis-aryl fragment and Sonogashira reaction for the delta- bond of the central amino-acid chain. The compound is a potent inhibitor of thrombin's activities in vitro and demonstrates potent oral anti-thrombotic potencies in three rat models of thrombosis. The observed in vitro potency could be rationalized through the examination of the interactions within the SSR182289A 1 - thrombin crystal structure. SSR182289A 1, has been therefore selected for further development.