Aminotriazine 5-HT7 antagonists

The present studies have identified a series of aminotriazines as novel 5-HT(7) receptor antagonists. Compounds 10 and 17 have high affinity for the 5-HT(7) receptor and do not bind to either the 5-HT(2C) or 5-HT(6) receptors. These compounds produce no agonist effects by themselves, and shift the dose-response curve of 5-CT to the right in the manner of an antagonist.     

Fgf signaling instructs position-dependent growth rate during zebrafish fin regeneration

During appendage regeneration in urodeles and teleosts, tissue replacement is precisely regulated such that only the appropriate structures are recovered, a phenomenon referred to as positional memory. It is believed that there exists, or is quickly established after amputation, a dynamic gradient of positional information along the proximodistal (PD) axis of the appendage that assigns region-specific instructions to injured tissue. These instructions specify the amount of tissue to regenerate, as well as the rate at which regenerative growth is to occur. A striking theme among many species is that the rate of regeneration is more rapid in proximally amputated appendages compared with distal amputations. However, the underlying molecular regulation is unclear. Here, we identify position-dependent differences in the rate of growth during zebrafish caudal fin regeneration. These growth rates correlate with position-dependent differences in blastemal length, mitotic index and expression of the Fgf target genes mkp3, sef and spry4. To address whether PD differences in amounts of Fgf signaling are responsible for position-dependent blastemal function, we have generated transgenic fish in which Fgf receptor activity can be experimentally manipulated. We find that the level of Fgf signaling exhibits strict control over target gene expression, blastemal proliferation and regenerative growth rate. Our results demonstrate that Fgf signaling defines position-dependent blastemal properties and growth rates for the regenerating zebrafish appendage.     

Population Dynamics and Rates of Molecular Evolution of a Recently Emerged Paramyxovirus, Avian Metapneumovirus Subtype C

We report the existence of two distinct sublineages of avian metapneumovirus (MPV) subtype C, a virus which has caused serious economic loss in commercial turkey farms in the United States. This subtype is closely related to human MPV, infects multiple avian species, and is globally distributed. The evolutionary rates of this virus are estimated to be 1.3 × 10⁻³ to 7 × 10⁻³ substitutions per site per year, and coalescent estimates place its emergence between 1991 and 1996. The four genes examined show a concordant demographic pattern which is characterized by a rapid increase in population size followed by stable population grown until the present.     

Genetic consequences of sex-biased dispersal in a solitary carnivore: Yellowstone cougars

Male-biased dispersal is a common trait in mammals, including carnivores, but its genetic consequences at the population level have been rarely considered for solitary species. We used long-term genetic data from cougars (Puma concolor) in and around Yellowstone National Park to test predictions based on differences in dispersal behaviour among males and females. Consistent with frequent long-distance dispersal of males, we found support for our prediction of less than expected allele sharing in pair-wise comparisons. In contrast, female residents present at the same time and females separated by few generations failed to share more alleles than expected, contrary to our predictions based on limited female dispersal. However, we find that genetic contributions of females with higher reproductive success were still noticeable in subsequent generations, consistent with female offspring showing fidelity to their natal area. These results highlight the importance of male dispersal for inbreeding avoidance, but do not indicate that short-distance dispersal or philopatry in female cougars results in spatial clustering of related individuals.     

The Microbial Spectrum of Neonatal Sepsis in Uganda: Recovery of Culturable Bacteria in Mother-Infant Pairs

Neonatal sepsis in the developing world is incompletely characterized. We seek to characterize the microbial spectrum involved in sepsis and determine the role of maternal transmission by comparing organisms that can be cultured from septic newborn infants and their mothers. From 80 consecutive mother-infant pairs meeting clinical criteria for neonatal sepsis, we collected infant blood and spinal fluid, and maternal blood and vaginal specimens. Identifiable bacteria were recovered from the blood in 32.5% of infants, and from 2.5% of cerebrospinal fluid cultures, for a total of 35% recoverable putative causative agents. Bacteria recovered from vaginal specimens were not concordant with those recovered from infants. Similarly there was no concordance of bacteria recovered from blood and cerebrospinal fluid. We conclude that relying on traditional bacterial culture techniques does not adequately delineate the role of maternal versus environmental sources of neonatal sepsis in this setting. More sensitive molecular approaches will be needed to properly characterize the maternal and environmental microbial community involved in neonatal sepsis in such developing countries.     

Results of a Free Spay/Neuter Program in a Hispanic Colonia on the Texas-Mexico Border

The purpose of this study, conducted in a small, impoverished Hispanic community on the Texas-Mexico border, was to evaluate the level of participation in a bilingual spay/neuter program offered free of charge to residents with companion animals. Prior to the sterilization project, approximately 11% of dogs and about 27% of cats with guardians underwent surgical sterilization. Over an 8-month period, the spay/neuter program sterilized about 47% of dogs and 38% of cats who had guardians in the community. In spite of residents' early reluctance to neuter their dogs, the project sterilized nearly equal numbers of male and female dogs (200 male; 201 female).     

Pyrrolo[1,2-f]triazines as JAK2 inhibitors: achieving potency and selectivity for JAK2 over JAK3

SAR studies of pyrrolo[1,2-f]triazines as JAK2 inhibitors is presented. Achieving JAK2 inhibition selectively over JAK3 is discussed.     

pH dependent salinity-boron interactions impact yield, biomass, evapotranspiration and boron uptake in broccoli (Brassica oleracea L.)

Aims

Soil pH is known to influence many important biochemical processes in plants and soils, however its role in salinity—boron interactions affecting plant growth and ion relations has not been examined. The purpose of this research was to evaluate the interactive effects of salinity, boron and soil solution pH on broccoli (Brassica oleracea L.) growth, yield, consumptive water use and shoot-boron accumulation.

Methods

A greenhouse experiment was conducted using a sand tank system where salinity-B-pH treatment solutions were supplemented with a complete nutrient solution. Sulfate-dominated irrigation waters, characteristic of groundwater in California’s San Joaquin valley (SJV), were tested at EC levels of 2, 5, 8, 11 and 14 dS?m^?1. Each salinity treatment consisted of two boron treatments (0.5 and 21 mg?L^?1) and each of those treatments was tested under slightly basic (pH?8.0) and slightly acidic (pH?6.0) conditions.

Results

Results included multiple salinity-boron-pH interactions affecting shoot biomass, head yield and consumptive water use. Broccoli fresh head yields were significantly reduced by salinity and boron, but the degree of yield reductions was influenced by pH. Relative head yields were substantially reduced in treatments with high pH and high B, particularly under low and high salinity where head yields were decreased by 89 % and 96 %, respectively, relative to those at low salinity and low boron. Intermediate levels of salinity were far less damaging. Increased salinity and boron reduced evapotranspiration (ET) and there were no salinity-boron associated interactions on ET. However, increased salinity and boron concentrations increased water use efficiency (shoot biomass/cumulative volume ET). Shoot B concentration increased with increased boron and was greater at pH?6 as compared to pH?8. Shoot boron concentration decreased with increasing salinity at both pH levels but particularly at the high substrate boron concentration.

Conclusions

It is likely that different mechanisms, yet unknown, are responsible for severe head-yield reductions at low and high salinity in the presence of high boron under alkaline conditions. We found that boron in the shoot did not accumulate by a simple passive process. Rather as boron increased from 0.5 to 21 mg?L^?1, there was a restrictive mechanism where total shoot boron (mg plant^?1) was reduced by 10 to 40 times the amount potentially supplied to the shoot by passive transport via mass flow perhaps involving complex interactions with membrane channels and B exporters. Total shoot boron concentration was a poor indicator of plant growth response.