Biogeographical conditions, the transition to agriculture and long-run growth

We use new data on the timing of the transition to agriculture, developed by Putterman and Trainor (2006), to test the theory of Diamond (1997) and Olsson and Hibbs (2005) that an earlier transition is reflected in higher incomes today. Our results confirm the theory, even after controlling for institutional quality and other geographical factors. The date of transition is correlated with prehistoric biogeography (the availability of wild grasses and large domesticable animal species). The factors conducive to high per capita incomes today are good institutions, an early transition to agriculture, access to the sea and a low incidence of fatal malaria. Geographical influences have been at work in all of these proximate determinants of per capita income.

A survey of molecular line emission towards ultracompact HII regions

We have used the JCMT to survey molecular line emission towards 14 ultracompact HII regions (G5.89, G9.62, G10.30, G10.47, G12.21, G13.87, G29.96, G31.41, G34.26, G43.89, G45.12, G45.45, G45.47, and G75.78). For each source, we observed up to ten 1 GHz bands between 200 and 350 GHz, covering lines of more than 30 species including multiple transitions of CO isotopes, CH3OH, CH3CCH, CH3CN and HCOOCH3, and sulphuretted molecules. The number of transitions detected varied by a factor of 20 between sources; which were chosen following observations of high-excitation ammonia (Cesaroni et al. 1994a) and methyl cyanide (Olmi et al. 1993). In half our sample (the line-poor sources), only (CO)-O-17: (CO)-O-18, SO, (CS)-S-34 and CH3OH were detected. In the line-rich sources, we detected over 150 lines, including high excitation lines of CH3CN, HCOOCH3; C2H5CN, CH3OH, and CH3CCH. We have calculated the physical conditions of the molecular gas. To reproduce the emission from the line-rich sources requires both a hot, dense compact core and an ambient cloud consisting of less dense, cooler gas. The hot cores, which are less than 0.1 pc in size; reach densities of at least 10(8) cm(-3) and temperatures of more than 80 K. The line-poor sources can be modelled without a hot core by a 20-30 K, 10(5) cm(-3) cloud. We find no correlation between the size of the HII region and the current physical conditions in the molecular environment. A comparison with chemical models (Millar et al. 1997) confirms that grain surface chemistry is important in hot cores.

IMMUNOREACTIVITY TO 2 SPECIFIC REGIONS OF CHROMOGRANIN-A IN THE NERVOUS-SYSTEM OF ASCARIS-SUUM - AN IMMUNOCYTOCHEMICAL STUDY

Antisera to a highly conserved region of chromogranin A (sequence KELTAE) and to a hexapeptide (sequence KGQELE) adjacent to the putative C-terminus of pancreastatin, a peptide whose sequence is found within the chromogranin A molecule, have been used to examine the localisation of immunoreactivity (IR) to these peptides in Ascaris suum. IR to both peptides was found in the nerve rings and nerve cords. In addition, KGQELE-IR was also observed in the pharyngeal neurones and in a network of fibres on the surface of the female gonoduct. The staining was specific in that it could be abolished by preincubation of the antisera with the appropriate antigen. The two antisera appeared to be staining different subsets of neurones, suggesting that (at least) two peptides were being recognised. The widespread distribution of IR to both peptides throughout the nervous system of the parasite suggests that the peptides carrying the epitopes recognised by the antisera are of fundamental importance to the functioning of the parasite's nervous system.

Structure-Guided Investigation of Lipopolysaccharide O-Antigen Chain Length Regulators Reveals Regions Critical for Modal Length Control

The O-antigen component of the lipopolysaccharide (LPS) represents a population of polysaccharide molecules with nonrandom (modal) chain length distribution. The number of the repeat O units in each individual O-antigen polymer depends on the Wzz chain length regulator, an inner membrane protein belonging to the polysaccharide copolymerase (PCP) family. Different Wzz proteins confer vastly different ranges of modal lengths (4 to > 100 repeat units), despite having remarkably conserved structural folds. The molecular mechanism responsible for the selective preference for a certain number of O units is unknown. Guided by the three-dimensional structures of PCPs, we constructed a panel of chimeric molecules containing parts of two closely related Wzz proteins from Salmonella enterica and Shigella flexneri which confer different O-antigen chain length distributions. Analysis of the O-antigen length distribution imparted by each chimera revealed the region spanning amino acids 67 to 95 (region 67 to 95), region 200 to 255, and region 269 to 274 as primarily affecting the length distribution. We also showed that there is no synergy between these regions. In particular, region 269 to 274 also influenced chain length distribution mediated by two distantly related PCPs, WzzB and FepE. Furthermore, from the 3 regions uncovered in this study, region 269 to 274 appeared to be critical for the stability of the oligomeric form of Wzz, as determined by cross-linking experiments. Together, our data suggest that chain length determination depends on regions that likely contribute to stabilize a supramolecular complex.

An anthrax subunit vaccine candidate based on protective regions of Bacillus anthracis protective antigen and lethal factor

Studies have confirmed the key role of Bacillus anthracis protective antigen (PA) in the US and UK human anthrax vaccines. However, given the tripartite nature of the toxin, other components, including lethal factor (LF), are also likely to contribute to protection. We examined the antibody and T cell responses to PA and LF in human volunteers immunized with the UK anthrax vaccine (AVP). Individual LF domains were assessed for immunogenicity in mice when given alone or with PA. Based on the results obtained, a novel fusion protein comprising D1 of LF and the host cell-binding domain of PA (D4) was assessed for protective efficacy. Murine protection studies demonstrated that both full-length LF and D1 of LF conferred complete protection against a lethal intraperitoneal challenge with B. anthracis STI spores. Subsequent studies with the LFD1-PAD4 fusion protein showed a similar level of protection. LF is immunogenic in humans and is likely to contribute to the protection stimulated by AVP. A single vaccine comprising protective regions from LF and PA would simplify production and confer a broader spectrum of protection than that seen with PA alone.

A novel dual-fluorescence strategy for functionally validating microRNA targets in 3-prime untranslated regions: regulation of the inward rectifier potassium channel Kir2.1 by miR-212.

Gene targeting by microRNAs is important in health and disease. We developed a functional assay for identifying microRNA targets and applied it to the K+ channel Kir2.1 (KCNJ2) which is dysregulated in cardiac and vascular disorders. The 3'UTR was inserted downstream of the mCherry red fluorescent protein coding sequence in a mammalian expression plasmid. MicroRNA sequences were inserted into the pSM30 expression vector which provides enhanced green fluorescent protein as an indicator of microRNA expression. HEK293 cells were co-transfected with the mCherry-3'UTR plasmid and a pSM30-based plasmid with a microRNA insert. The principle of the assay is that functional targeting of the 3'UTR by the microRNA results in a decrease in the red/green fluorescence intensity ratio as determined by automated image analysis. The method was validated with miR-1, a known downregulator of Kir2.1 expression, and was used to investigate targeting of the Kir2.1 3'UTR by miR-212. Red/green ratio was lower in miR-212-expressing cells compared to non-targeting controls, an effect that was attenuated by mutating the predicted target site. MiR-212 also reduced inward rectifier current and Kir2.1 protein in HeLa cells. This novel assay has several advantages over traditional luciferase-based assays including larger sample size, amenability to time course studies and adaptability to high-throughput screening.