Localization of the β-globin gene to 11p15 by in situ hybridization: Utilization of chromosome 11 rearrangements

Summary Chromosome preparations from four subjects, one normal 46,XY male and three patients with different rearrangements of chromosome 11:46,XX,del(11)(p11.2p15.1), 46,XY,inv(11)(p13q24.2), and 46,XY,rec(11)inv(11)(p13q24.2) pat, were utilized for in situ hybridization studies with a tritium-labeled cDNA probe containing a -globin insert. Using the hybridization technique described by Harper and Saunders (1981), there were 1–2 grains over each labeled metaphase. Of 360 cells scored, 88 were labeled over chromosome 11, band p15 (24%). Approximately half of the chromosome 11s labeled from the abnormal patients were the del(11) or inv(11). These results exclude the -globin locus from 11p11p14, since these bands were not present in the recent 11, and assign it to 11p15. This is in agreement with the recent exclusion data of de Martiville and Francke (1984) and Junien (1984), and suggestive assignment data of Morton et al. (1984).     

Effect of Arginine on the Aggregation of Protein in Freeze-Dried Formulations Containing Sugars and Polyol: II. BSA Reconstitution and Aggregation

The current paper continues our study on the ability of l-arginine to prevent/reduce the aggregation of proteins that results from the various stresses during the lyophilisation and/or storage of lyophilized protein-based products. The first part of our study, i.e. formulation development, was devoted to the rational design and optimization of an l-arginine containing lyophilized formulation which can resist the natural tendency of l-arginine to absorb atmosphere moisture. Mannitol and trehalose were chosen among other excipients to be included in the protein-based formulation, as mannitol in a combination with l-arginine has been shown to reduce moisture sorption while trehalose provides a degree of lyoprotection. In the present study, a number of formulations, which comprised bovine serum albumin (BSA) with and without l-arginine, and with five different ratios of trehalose-to-mannitol (from 30:70 to 80:20) were lyophilised and assessed. The internal structures and the moisture sorption/retention of the lyophilized formulations were characterised. To study the effect of l-arginine on BSA solid-phase stability, the lyophilized powder was exposed to accelerated storage conditions (high moisture (75% RH) and temperature (22 or 45 °C)) for up to 24 h. The lyophilized BSA formulations were then reconstituted and solution-state protein aggregation assessed by turbidimetry at 360 nm and fluorescence spectroscopy using the thioflavin T assay. It was demonstrated that l-arginine can be used in protein-based freeze-dried formulations to significantly reduce the aggregation of protein during the manufacturing, storage and subsequent reconstitution. The results also revealed the importance of a sufficient amount of mannitol in the arginine-containing formulations.     

A Simplified Geometric Model to Predict Nasal Spray Deposition in Children and Adults

A mathematical approach was developed to estimate spray deposition patterns in the nasal cavity based on the geometric relationships between the emitted spray plume and the anatomical dimensions of the nasal valve region of the nasal cavity. Spray plumes were assumed to be spherical cones and the nasal valve region was approximated as an ellipse. The effect of spray plume angle (15–85°) on the fraction of the spray able to pass through the nasal valve (deposition fraction) was tested for a variety of nasal valve (ellipse) shapes and cross-sectional areas based on measured dimensions from pediatric and adult nasal cavities. The effect of the distances between the tip of the nasal spray device and the nasal valve (0.2–1.9 cm) on the deposition fraction was also tested. Simulation results show that (1) decreasing spray plume angles resulted in higher deposition fractions, (2) deposition fraction was inversely proportional to the spray distance and the nasal valve (ellipse) major/minor axis ratio, and (3) for fixed major/minor axis ratios, improved deposition occurred with larger nasal valve cross-sectional areas. For a typical adult nasal valve, plume angles of less than 40° emitted from a distance of 1 cm resulted depositions greater than 90% within the main nasal cavity, whereas for a 12-year-old child, only the most narrow plume angles (<?20°) administered resulted in significant deposition beyond the nasal valve.     

Using Bloodmeal Analysis to Assess Disease Risk to Wildlife at the New Northern Limit of a Mosquito Species

The historically southeastern mosquito species Culex erraticus has over the last 30 years undergone a marked expansion north. We evaluated this species’ potential to participate in local disease cycles in the northeastern USA by identifying the vertebrate sources of blood in Cx. erraticus specimens from New Jersey. We found that the majority of bloodmeals (92.6%) were derived from birds, followed by 6.8% from mammals (of which half were human), and a single amphibian bloodmeal from a spring peeper (0.56%). Medium- and large-sized water birds from the order Pelecaniformes made up 60.4% of the bird species and 55.9% of all identified hosts. This group of birds is known enzootic hosts of arboviruses such as eastern equine encephalitis virus, for which Cx. erraticus is a competent vector. Additionally, we screened blooded mosquitoes for avian malaria parasites and identified three different lineages of Plasmodium, including what may represent a new Plasmodium species (likely a wetland bird specialist) in bloodmeals from Green Herons, a Great Egret, and a Double-Crested Cormorant. Our results support the utility of mosquito bloodmeals as sources of information about circulating wildlife pathogens and reveal the potential of range-expanding species to intensify local zoonoses and bridge enzootic pathogens to humans.     

Drought reduces floral resources for pollinators

Climate change is predicted to result in increased occurrence and intensity of drought in many regions worldwide. By increasing plant physiological stress, drought is likely to affect the floral resources (flowers, nectar and pollen) that are available to pollinators. However, little is known about impacts of drought at the community level, nor whether plant community functional composition influences these impacts. To address these knowledge gaps, we investigated the impacts of drought on floral resources in calcareous grassland. Drought was simulated using rain shelters and the impacts were explored at multiple scales and on four different experimental plant communities varying in functional trait composition. First, we investigated the effects of drought on nectar production of three common wildflower species (Lathyrus pratensis, Onobrychis viciifolia and Prunella vulgaris). In the drought treatment, L. pratensis and P. vulgaris had a lower proportion of flowers containing nectar and O. viciifolia had fewer flowers per raceme. Second, we measured the effects of drought on the diversity and abundance of floral resources across plant communities. Drought reduced the abundance of floral units for all plant communities, irrespective of functional composition, and reduced floral species richness for two of the communities. Functional diversity did not confer greater resistance to drought in terms of maintaining floral resources, probably because the effects of drought were ubiquitous across component plant communities. The findings indicate that drought has a substantial impact on the availability of floral resources in calcareous grassland, which will have consequences for pollinator behaviour and populations.     

Experiences with the Mass Distribution of LPG Stoves in Rural Communities of Ghana

Household air pollution (HAP) is a leading cause of morbidity and mortality worldwide. To limit HAP exposure and environmental degradation from biomass fuel use, the Government of Ghana promotes liquefied petroleum gas (LPG) use in rural Ghana via the Rural LPG program (RLP). We assessed the experiences of the RLP in 2015, 2 years after its launch. A mixed methods approach was used involving Focus Group Discussions (19) and in-depth interviews (25). In addition, a survey questionnaire was administered to elicit socio-demographic characteristics, household cooking practices and stove use patterns of 200 randomly selected respondents. At about 9 months after LPG acquisition,?<?5% of LPG beneficiaries used their stoves. Some of the reasons ascribed to the low usage of the LPG cookstoves were financial constraints, distance to LPG filling point and fear of burns. Community members appreciate the convenience of using LPG. Our results underscore a need for innovative funding mechanisms contextualized within an overall economic empowerment of rural folks to encourage sustained LPG use. It emphasizes the need for innovative accessibility interventions. This could include establishing new LPG filling stations in RLP beneficiary districts to overcome the barriers to sustained LPG use.     

Dung beetles and their ecological functions in three agroforestry systems in the Lacandona rainforest of Mexico

There is growing interest in evaluating the impact that management intensity of agroecosystems has on animal communities and their ecological functions. Dung beetles are a highly used focal taxon for assessing the effects of anthropogenic disturbances and management practices on biodiversity. In the Lacandona rainforest region in southern Mexico, we quantified several metrics of the dung beetle community (number of species, number of individuals, total biomass, mean beetle size) and four of their ecological functions (dung removal, soil excavation, seed dispersal, seed exhumation) in conserved rainforest and three agroforestry systems with different management intensities: rustic cocoa, polyculture cocoa, and rubber monoculture. We also assessed the correlation between dung removal and the other functions, as well as the relationships between functions and community metrics. Land-use type affected the dung beetle communities as well as their functions, with negative effects on response variables in the most intensely managed agroecosystems (polyculture cocoa and rubber). Rustic cocoa had values similar to those of the conserved forest for all functions and community metrics, except the mean number of species per trap. Dung removal was correlated with the other ecological functions. The mean number of species per trap was significantly associated with all four functions. In our study region rustic cocoa plantations favor the maintenance of a high proportion of dung beetle species and maintain their ecological functions. Our findings corroborate that agroecosystems with less intense management may contribute to buffering the effects of landscape homogenization caused by more intensely managed agroecosystems, such as rubber plantations.     

Investigating small molecules to inhibit germinal center kinase-like kinase (GLK/MAP4K3) upstream of PKCθ phosphorylation: Potential therapy to modulate T cell dependent immunity

Germinal center kinase-like kinase (GLK, also known as MAP4K3) has been hypothesized to have an effect on key cellular activities, including inflammatory responses. GLK is required for activation of protein kinase C-θ (PKCθ) in T cells. Controlling the activity of T helper cell responses could be valuable for the treatment of autoimmune diseases. This approach circumvents previous unsuccessful approaches to target PKCθ directly. The use of structure based drug design, aided by the first crystal structure of GLK, led to the discovery of several inhibitors that demonstrate potent inhibition of GLK biochemically and in relevant cell lines.