“I Hate White People!”—Subverting the Televisual Gaze

I have previously argued that the other viewing the Self highlights the ramifications of the question “Who are they?” vis-à-vis notions of “Who are we?” and that the answer to the former directly shapes and informs the latter, as Fourth World people are forced to negotiate their identity upon exposure to First World television. In this article, I examine a particular group of subaltern viewers who reassign the roles of self and Other in order to preserve, defend, and construct their own selfhood. Because they look and act differently from those in the mediated mainstream, Navajo television viewers create oppositional identities by understanding themselves first in relation to and then opposed to standardized models. Subverting the televisual gaze is their way of articulating experiences of powerlessness in a white-dominated society as well as a means of communicating a discourse of resistance to the dominant ideology.     

Establishment of a Captive All‐male Group of Proboscis Monkey (Nasalis larvatus) at the Singapore Zoo

Surplus male proboscis monkeys at the Singapore Zoo pose a considerable problem for maintenance and maximizing of exhibition potential. In 2008, a new exhibit was constructed to house and display a group of six proboscis monkey males born in Singapore Zoo. To document and monitor the all‐male group establishment in the new exhibit, we conducted observations on intragroup interactions between the monkeys, spatial use of their new exhibit, and visitor effects on their behavior. We found contact aggressive interactions between the monkeys to be consistently lower than noncontact aggressive interactions and by week six of introduction to the new exhibit, contact aggression was almost nonevident. Affiliative interactions also developed between individuals in the group, with an interface of aggressive and socioreconcilatory behavior influenced by food competition and a dominance hierarchy. This was evident from significantly higher overall aggression and affiliation during feeding times compared to nonfeeding times, and this was reduced when food competition was mitigated by modifying the feeding regime. We measured the groups’ spatial use of the exhibit and the relation to behavior, crowd size, and density. Our results showed that the proboscis monkeys utilized the available exhibit space, were largely unaffected by visitor crowd size and density, and were able to exhibit a variety of natural behaviors, including swimming. Our accomplishment in maintaining and displaying an all‐male group of proboscis monkeys in captivity provides viable options for more comprehensive captive management and breeding programs for this endangered species. Zoo Biol. 32:281‐290, 2013. © 2012 Wiley Periodicals, Inc.     

Characterization of the Staphylococcus aureus rRNA Methyltransferase Encoded by orfX,the Gene Containing the Staphylococcal Chromosome Cassette mec (SCCmec) Insertion Site

The gene orfX is conserved among all staphylococci, and its complete sequence is maintained upon insertion of the staphylococcal chromosome cassette mec (SCCmec) genomic island, containing the gene encoding resistance to β-lactam antibiotics (mecA), into its C terminus. The function of OrfX has not been determined. We show that OrfX was constitutively produced during growth, that orfX could be inactivated without altering bacterial growth, and that insertion of SCCmec did not alter gene expression. We solved the crystal structure of OrfX at 1.7 Å and found that it belongs to the S-adenosyl-l-methionine (AdoMet)-dependent α/β-knot superfamily of SPOUT methyltransferases (MTases), with a high structural homology to YbeA, the gene product of the Escherichia coli 70 S ribosomal MTase RlmH. MTase activity was confirmed by demonstrating the OrfX-dependent methylation of the Staphylococcus aureus 70 S ribosome. When OrfX was crystallized in the presence of its AdoMet substrate, we found that each monomer of the homodimeric structure bound AdoMet in its active site. Solution studies using isothermal titration calorimetry confirmed that each monomer bound AdoMet but with different binding affinities (K_d = 52 ± 0.4 and 606 ± 2 μm). In addition, the structure shows that the AdoMet-binding pocket, formed by a deep trefoil knot, contains a bound phosphate molecule, which is the likely nucleotide methylation site. This study represents the first characterization of a staphylococcal ribosomal MTase and provides the first crystal structure of a member of the α/β-knot superfamily of SPOUT MTases in the RlmH or COG1576 family with bound AdoMet.     

Optogenetic control of cell function using engineered photoreceptors

Over the past decades, there has been growing recognition that light can provide a powerful stimulus for biological interrogation. Light‐actuated tools allow manipulation of molecular events with ultra‐fine spatial and fast temporal resolution, as light can be rapidly delivered and focused with sub‐micrometre precision within cells. While light‐actuated chemicals such as photolabile ‘caged’ compounds have been in existence for decades, the use of genetically encoded natural photoreceptors for optical control of biological processes has recently emerged as a powerful new approach with several advantages over traditional methods. Here, we review recent advances using light to control basic cellular functions and discuss the engineering challenges that lie ahead for improving and expanding the ever‐growing optogenetic toolkit.     

Caspase‐7 participates in differentiation of cells forming dental hard tissues

Apoptosis during tooth development appears dependent on the apoptotic executioner caspase‐3, but not caspase‐7. Instead, activated caspase‐7 has been found in differentiated odontoblasts and ameloblasts, where it does not correlate with apoptosis. To further investigate these findings, the mouse incisor was used as a model. Analysis of caspase‐7‐deficient mice revealed a significant thinner layer of hard tissue in the adult incisor. Micro computed tomography scan confirmed this decrease in mineralized tissues. These data strongly suggest that caspase‐7 might be directly involved in functional cell differentiation and regulation of the mineralization of dental matrices.     

Gene Content and Diversity of the Loci Encoding Biosynthesis of Capsular Polysaccharides of the 15 Serovar Reference Strains of Haemophilus parasuis

Haemophilus parasuis is the causative agent of Glässer''s disease, a systemic disease of pigs, and is also associated with pneumonia. H. parasuis can be classified into 15 different serovars. Here we report, from the 15 serotyping reference strains, the DNA sequences of the loci containing genes for the biosynthesis of the group 1 capsular polysaccharides, which are potential virulence factors of this bacterium. We contend that these loci contain genes for polysaccharide capsule structures, and not a lipopolysaccharide O antigen, supported by the fact that they contain genes such as wza, wzb, and wzc, which are associated with the export of polysaccharide capsules in the current capsule classification system. A conserved region at the 3′ end of the locus, containing the wza, ptp, wzs, and iscR genes, is consistent with the characteristic export region 1 of the model group 1 capsule locus. A potential serovar-specific region (region 2) has been found by comparing the predicted coding sequences (CDSs) in all 15 loci for synteny and homology. The region is unique to each reference strain with the exception of those in serovars 5 and 12, which are identical in terms of gene content. The identification and characterization of this locus among the 15 serovars is the first step in understanding the genetic, molecular, and structural bases of serovar specificity in this poorly studied but important pathogen and opens up the possibility of developing an improved molecular serotyping system, which would greatly assist diagnosis and control of Glässer''s disease.     

Development of an in vivo active,dual EP1 and EP3 selective antagonist based on a novel acyl sulfonamide bioisostere

Recent preclinical studies demonstrate a role for the prostaglandin E₂ (PGE₂) subtype 1 (EP1) receptor in mediating, at least in part, the pathophysiology of hypertension and diabetes mellitus. A series of amide and N-acylsulfonamide analogs of a previously described picolinic acid-based human EP1 receptor antagonist (7) were prepared. Each analog had improved selectivity at the mouse EP1 receptor over the mouse thromboxane receptor (TP). A subset of analogs gained affinity for the mouse PGE₂ subtype 3 (EP3) receptor, another potential therapeutic target. One analog (17) possessed equal selectivity for EP1 and EP3, displayed a sufficient in vivo residence time in mice, and lacked the potential for acyl glucuronide formation common to compound 7. Treatment of mice with 17 significantly attenuated the vasopressor activity resulting from an acute infusion of EP1 and EP3 receptor agonists. Compound 17 represents a potentially novel therapeutic in the treatment of hypertension and diabetes mellitus.     

Conformational restriction in a series of GPR119 agonists: Differences in pharmacology between mouse and human

A series of conformationally restricted GPR119 agonists were prepared based around a 3,8-diazabicyclo[3.2.1]octane scaffold. Examples were found to have markedly different pharmacology in mouse and human despite similar levels of binding to the receptor. This highlights the large effects on GPCR phamacology that can result from small structural changes in the ligand, together with inter-species differences between receptors.     

Synthesis and bioevaluation of [18F]4-fluoro-m-hydroxyphenethylguanidine ([18F]4F-MHPG): A novel radiotracer for quantitative PET studies of cardiac sympathetic innervation

A new cardiac sympathetic nerve imaging agent, [¹⁸F]4-fluoro-m-hydroxyphenethylguanidine ([¹⁸F]4F-MHPG), was synthesized and evaluated. The radiosynthetic intermediate [¹⁸F]4-fluoro-m-tyramine ([¹⁸F]4F-MTA) was prepared and then sequentially reacted with cyanogen bromide and NH₄Br/NH₄OH to afford [¹⁸F]4F-MHPG. Initial bioevaluations of [¹⁸F]4F-MHPG (biodistribution studies in rats and kinetic studies in the isolated rat heart) were similar to results previously reported for the carbon-11 labeled analog [¹¹C]4F-MHPG. The neuronal uptake rate of [¹⁸F]4F-MHPG into the isolated rat heart was 0.68 ml/min/g wet and its retention time in sympathetic neurons was very long (T_1/2 >13 h). A PET imaging study in a nonhuman primate with [¹⁸F]4F-MHPG provided high quality images of the heart, with heart-to-blood ratios at 80–90 min after injection of 5-to-1. These initial kinetic and imaging studies of [¹⁸F]4F-MHPG suggest that this radiotracer may allow for more accurate quantification of regional cardiac sympathetic nerve density than is currently possible with existing neuronal imaging agents.     

Comparison of historical bottleneck effects and genetic consequences of re‐introduction in a critically endangered island passerine

Re‐introduction is an important tool for recovering endangered species; however, the magnitude of genetic consequences for re‐introduced populations remains largely unknown, in particular the relative impacts of historical population bottlenecks compared to those induced by conservation management. We characterize 14 microsatellite loci developed for the Seychelles paradise flycatcher and use them to quantify temporal and spatial measures of genetic variation across a 134‐year time frame encompassing a historical bottleneck that reduced the species to ~28 individuals in the 1960s, through the initial stages of recovery and across a second contemporary conservation‐introduction‐induced bottleneck. We then evaluate the relative impacts of the two bottlenecks, and finally apply our findings to inform broader re‐introduction strategy. We find a temporal trend of significant decrease in standard measures of genetic diversity across the historical bottleneck, but only a nonsignificant downward trend in number of alleles across the contemporary bottleneck. However, accounting for the different timescales of the two bottlenecks (~40 historical generations versus <1 contemporary generation), the loss of genetic diversity per generation is greater across the contemporary bottleneck. Historically, the flycatcher population was genetically structured; however, extinction on four of five islands has resulted in a homogeneous contemporary population. We conclude that severe historical bottlenecks can leave a large footprint in terms of sheer quantity of genetic diversity lost. However, severely depleted genetic diversity does not render a species immune to further genetic erosion upon re‐introduction. In some cases, the loss of genetic diversity per generation can, initially at least, be greater across re‐introduction‐induced bottlenecks.