From connection to contagion

This essay proposes that we ‘think data’ with a complex legacy of work, once disavowed and now resurgent in social theory, on crowd formations. I propose this move because social media platforms’ mobilization of data – the extractions, ever-shifting reaggregations, and micro-targeting, on the one hand, and our engagements, re-tweets, acts of sharing, and production of virality, on the other – has fuelled such anxious concern about the very things that animated much crowd theory in the first place. Key among these concerns are the force of emotional contagion and the threat of social dissolution; the composition of ‘the social’ by elements that well exceed the human; and pressing questions about the media through which energetic forces travel, often with lightning speed. What questions might be enabled by attending to the resonance between crowd theory's ‘anti-liberal’ preoccupations and contemporary concerns over how social media platforms crowd us?     

Substrate and metal specificity in the enzymic synthesis of cyclic monoterpenes from geranyl and neryl pyrophosphate

A partially purified enzyme (carbocyclase) from the flavedo of Citrus limonum formed α-pinene, β-pinene, limonene, and γ-terpinene from geranyl pyrophosphate (GPP) and neryl pyrophosphate. The maximum specific activities obtained were 7.0 and 3.6 nmol/ min/mg, respectively. Cross-inhibition by the two substrates were observed and the ability to utilize neryl pyrophosphate was almost completely lost with aging. Citronellyl pyrophosphate and dimethylallyl pyrophosphate were the most effective inhibitors of carbocyclase. Isopentenyl pyrophosphate, the monophosphate esters of nerol and geraniol, as well as inorganic pyrophosphate were much less effective inhibitors. The enzyme had an absolute requirement for Mn²⁺. It could be replaced with about 2% effectiveness by Mg²⁺ and Co²⁺. Kinetic studies showed that the observed reaction rate correlates with the calculated concentration of the GPP (Mn²⁺)₂ species. Previous evidence with nonenzymatic reactions and the results presented support the view that the mechanism of carbocyclase may be the intramolecular analog of prenyltransferase.     

The Incidence Patterns Model to Estimate the Distribution of New HIV Infections in Sub-Saharan Africa: Development and Validation of a Mathematical Model

BackgroundProgrammatic planning in HIV requires estimates of the distribution of new HIV infections according to identifiable characteristics of individuals. In sub-Saharan Africa, robust routine data sources and historical epidemiological observations are available to inform and validate such estimates.ConclusionsIt is possible to reliably predict the distribution of new HIV infections acquired using data routinely available in many countries in the sub-Saharan African region with a single relatively simple mathematical model. This tool would complement more specific analyses to guide resource allocation, data collection, and programme planning.     

Thermoregulation and roost selection by reproductive female big brown bats (Eptesicus fuscus) roosting in rock crevices

A free-ranging maternity colony of big brown bats Eptesicus fuscus roosting in rock crevices along the South Saskatchewan River in south-eastern Alberta, Canada, was studied to understand better the discrepancy that exists in the literature regarding torpor use by reproductive female bats. Using radio-telemetry, thermoregulatory patterns and roost microclimate were recorded for pregnant, lactating and post-lactating females. Relative torpor use is described in several ways: the proportion of days on which torpor was used, depth, minimum body temperature, time spent in torpor, and a comprehensive torpor unit (degree-min). Pregnant and lactating female E. fuscus used torpor to the same extent overall (degree-min), but pregnant bats used torpor less frequently and with more time in deep torpor. Torpor was used to the greatest extent after weaning (post-lactation). Evidence is presented that the cost:benefit ratio for deep and prolonged periods of torpor may be highest during lactation. Microclimates of rock-crevice roosts mirrored the use of torpor throughout reproduction by bats. Lactation roosts (deeper, larger opening size) were more thermally stable and remained warmer at night compared to the shallow roosts used by pregnant and post-lactating females. It is shown that conclusions about relative use of torpor can differ depending on the units of comparison, necessitating measurement of all aspects of torpor (depth, duration and frequency). Comprehensive measurements, individual-based normothermic temperatures, and a definition of torpor that accounts for all energy savings, allow a more accurate depiction of patterns and facilitates inter-study comparisons.     

Enzymic aspects of the biosynthesis monoterpenes in plants

The biosynthesis of monoterpenes in higher plants is reviewed, with particular emphasis on recent studies of the enzymology of biosynthesis.     

Preclinical models for neuroblastoma: establishing a baseline for treatment

Background

Preclinical models of pediatric cancers are essential for testing newchemotherapeutic combinations for clinical trials. The most widely usedgenetic model for preclinical testing of neuroblastoma is the TH-MYCN mouse.This neuroblastoma-prone mouse recapitulates many of the features of humanneuroblastoma. Limitations of this model include the low frequency of bonemarrow metastasis, the lack of information on whether the gene expressionpatterns in this system parallels human neuroblastomas, the relatively slowrate of tumor formation and variability in tumor penetrance on differentgenetic backgrounds. As an alternative, preclinical studies are frequentlyperformed using human cell lines xenografted into immunocompromised mice,either as flank implant or orthtotopically. Drawbacks of this system includethe use of cell lines that have been in culture for years, the inappropriatemicroenvironment of the flank or difficult, time consuming surgery fororthotopic transplants and the absence of an intact immune system.

Principal Findings

Here we characterize and optimize both systems to increase their utility forpreclinical studies. We show that TH-MYCN mice develop tumors in theparaspinal ganglia, but not in the adrenal, with cellular and geneexpression patterns similar to human NB. In addition, we present a newultrasound guided, minimally invasive orthotopic xenograft method. Thisinjection technique is rapid, provides accurate targeting of the injectedcells and leads to efficient engraftment. We also demonstrate that tumorscan be detected, monitored and quantified prior to visualization usingultrasound, MRI and bioluminescence. Finally we develop and test a“standard of care” chemotherapy regimen. This protocol, which isbased on current treatments for neuroblastoma, provides a baseline forcomparison of new therapeutic agents.

Significance

The studies suggest that use of both the TH-NMYC model of neuroblastoma andthe orthotopic xenograft model provide the optimal combination for testingnew chemotherapies for this devastating childhood cancer.     

Alphavirus minus-strand RNA synthesis: identification of a role for Arg183 of the nsP4 polymerase

A partially conserved region spanning amino acids 142 to 191 of the Sindbis virus (SIN) nsP4 core polymerase is implicated in host restriction, elongation, and promoter recognition. We extended the analysis of this region by substituting Ser, Ala, or Lys for a highly conserved Arg183 residue immediately preceding its absolutely conserved Ser184-Ala-Val-Pro-Ser188 sequence. In chicken cells, the nsP4 Arg183 mutants had a nonconditionally lethal, temperature-sensitive (ts) growth phenotype caused by a ts defect in minus-strand synthesis whose extent varied with the particular amino acid substituted (Ser>Ala>Lys). Plus-strand synthesis by nsP4 Arg183 mutant polymerases was unaffected when corrected for minus-strand numbers, although 26S mRNA synthesis was enhanced at the elevated temperature compared to wild type. The ts defect was not due to a failure to form or accumulate nsP4 at 40 degrees C. In contrast to their growth in chicken cells, the nsP4 Arg183 mutants replicated equally poorly, if at all, in mosquito cells. We conclude that Arg183 within the Pro180-Asn-Ile-Arg-Ser184 sequence of the SIN nsP4 polymerase contributes to the efficient initiation of minus strands or the formation of its replicase and that a host factor(s) participates in this event.     

Multilocus and morphological analysis of south-eastern Iberian Wall lizards (Squamata,Podarcis)

The phylogenetic relationships among the wall lizards of the Podarcis hispanicus complex that inhabit the south-east (SE) of the Iberian Peninsula and other lineages of the complex remain unclear. In this study, four mitochondrial and two nuclear markers were used to study genetic relationships within this complex. The phylogenetic analyses based on mtDNA gene trees constructed with ML and BI, and a species tree using *BEAST support three divergent clades in this region: the Valencia, Galera and Albacete/Murcia lineages. These three lineages were also corroborated in species delimitation analyses based on mtDNA using bPTP, mPTP, GMYC, ABGD and BAPS. Bayesian inference species delimitation method (BPP) based on both nuclear data and a combined data set (mtDNA + nuclear) showed high posterior probabilities for these three SE lineages (≥0.94) and another Bayesian analysis (STACEY) based on combined data set recovered the same three groups in this region. Divergence time dating of the species tree provided an estimated divergence of the Galera lineage from the other SE group (Podarcis vaucheri, (Albacete/Murcia, Valencia)) at 12.48 Ma. During this period, the Betic–Rifian arc was isolated, which could have caused the isolation of the Galera form distributed to the south of the Betic Corridor. Although lizards from the Albacete/Murcia and Galera lineage are morphologically similar, they clearly represent distinct genetic lineages. The noteworthy separation of the Galera lineage enables us to conclude that this lineage must be considered as a new full species.