The promise and peril of intensive-site-based ecological research: insights from the Hubbard Brook ecosystem study

Abstract. Ecological research is increasingly concentrated at particular locations or sites. This trend reflects a variety of advantages of intensive, site-based research, but also raises important questions about the nature of such spatially delimited research: how well does site based research represent broader areas, and does it constrain scientific discovery?We provide an overview of these issues with a particular focus on one prominent intensive research site: the Hubbard Brook Experimental Forest (HBEF), New Hampshire, USA. Among the key features of intensive sites are: long-term, archived data sets that provide a context for new discoveries and the elucidation of ecological mechanisms; the capacity to constrain inputs and parameters, and to validate models of complex ecological processes; and the intellectual cross-fertilization among disciplines in ecological and environmental sciences. The feasibility of scaling up ecological observations from intensive sites depends upon both the phenomenon of interest and the characteristics of the site. An evaluation of deviation metrics for the HBEF illustrates that, in some respects, including sensitivity and recovery of streams and trees from acid deposition, this site is representative of the Northern Forest region, of which HBEF is a part. However, the mountainous terrain and lack of significant agricultural legacy make the HBEF among the least disturbed sites in the Northern Forest region. Its relatively cool, wet climate contributes to high stream flow compared to other sites. These similarities and differences between the HBEF and the region can profoundly influence ecological patterns and processes and potentially limit the generality of observations at this and other intensive sites. Indeed, the difficulty of scaling up may be greatest for ecological phenomena that are sensitive to historical disturbance and that exhibit the greatest spatiotemporal variation, such as denitrification in soils and the dynamics of bird communities. Our research shows that end member sites for some processes often provide important insights into the behavior of inherently heterogeneous ecological processes. In the current era of rapid environmental and biological change, key ecological responses at intensive sites will reflect both specific local drivers and regional trends

The Optical Design of CHARIS: An Exoplanet IFS for the Subaru Telescope

High-contrast imaging techniques now make possible both imaging and spectroscopy of planets around nearby stars. We present the optical design for the Coronagraphic High Angular Resolution Imaging Spectrograph (CHARIS), a lenslet-based, cryogenic integral field spectrograph (IFS) for imaging exoplanets on the Subaru telescope. The IFS will provide spectral information for 138x138 spatial elements over a 2.07 arcsec x 2.07 arcsec field of view (FOV). CHARIS will operate in the near infrared (lambda = 1.15 - 2.5 microns) and will feature two spectral resolution modes of R = 18 (low-res mode) and R = 73 (high-res mode). Taking advantage of the Subaru telescope adaptive optics systems and coronagraphs (AO188 and SCExAO), CHARIS will provide sufficient contrast to obtain spectra of young self-luminous Jupiter-mass exoplanets. CHARIS will undergo CDR in October 2013 and is projected to have first light by the end of 2015. We report here on the current optical design of CHARIS and its unique innovations.Comment: 15 page

Wholly Rickettsia! Reconstructed Metabolic Profile of the Quintessential Bacterial Parasite of Eukaryotic Cells

Reductive genome evolution has purged many metabolic pathways from obligate intracellular Rickettsia (Alphaproteobacteria; Rickettsiaceae). While some aspects of host-dependent rickettsial metabolism have been characterized, the array of host-acquired metabolites and their cognate transporters remains unknown. This dearth of information has thwarted efforts to obtain an axenic Rickettsia culture, a major impediment to conventional genetic approaches. Using phylogenomics and computational pathway analysis, we reconstructed the Rickettsia metabolic and transport network, identifying 51 host-acquired metabolites (only 21 previously characterized) needed to compensate for degraded biosynthesis pathways. In the absence of glycolysis and the pentose phosphate pathway, cell envelope glycocon- jugates are synthesized from three imported host sugars, with a range of additional host-acquired metabolites fueling the tricarboxylic acid cycle. Fatty acid and glycero- phospholipid pathways also initiate from host precursors, and import of both iso- prenes and terpenoids is required for the synthesis of ubiquinone and the lipid car- rier of lipid I and O-antigen. Unlike metabolite-provisioning bacterial symbionts of arthropods, rickettsiae cannot synthesize B vitamins or most other cofactors, accen- tuating their parasitic nature. Six biosynthesis pathways contain holes (missing en- zymes); similar patterns in taxonomically diverse bacteria suggest alternative en- zymes that await discovery. A paucity of characterized and predicted transporters emphasizes the knowledge gap concerning how rickettsiae import host metabolites, some of which are large and not known to be transported by bacteria. Collectively, our reconstructed metabolic network offers clues to how rickettsiae hijack host met- abolic pathways. This blueprint for growth determinants is an important step toward the design of axenic media to rescue rickettsiae from the eukaryotic cell

The Complete Genome Sequence of the Emerging Pathogen Mycobacterium haemophilum Explains Its Unique Culture Requirements

Mycobacterium haemophilum is an emerging pathogen associated with a variety of clinical syndromes, most commonly skin infections in immunocompromised individuals. M. haemophilum exhibits a unique requirement for iron supplementation to support its growth in culture, but the basis for this property and how it may shape pathogenesis is unclear. Using a combination of Illumina, PacBio, and Sanger sequencing, the complete genome sequence of M. haemophilum was determined. Guided by this sequence, experiments were performed to define the basis for the unique growth requirements of M. haemophilum. We found that M. haemophilum, unlike many other mycobacteria, is unable to synthesize iron-binding siderophores known as mycobactins or to utilize ferri-mycobactins to support growth. These differences correlate with the absence of genes associated with mycobactin synthesis, secretion, and uptake. In agreement with the ability of heme to promote growth, we identified genes encoding heme uptake machinery. Consistent with its propensity to infect the skin, we show at the whole-genome level the genetic closeness of M. haemophilumwith Mycobacterium leprae, an organism which cannot be cultivated in vitro, and we identify genes uniquely shared by these organisms. Finally, we identify means to express foreign genes in M. haemophilum. These data explain the unique culture requirements for this important pathogen, provide a foundation upon which the genome sequence can be exploited to improve diagnostics and therapeutics, and suggest use of M. haemophilum as a tool to elucidate functions of genes shared with M. leprae. IMPORTANCE Mycobacterium haemophilum is an emerging pathogen with an unknown natural reservoir that exhibits unique requirements for iron supplementation to grow in vitro. Understanding the basis for this iron requirement is important because it is fundamental to isolation of the organism from clinical samples and environmental sources. Defining the molecular basis for M. haemophilium\u27s growth requirements will also shed new light on mycobacterial strategies to acquire iron and can be exploited to define how differences in such strategies influence pathogenesis. Here, through a combination of sequencing and experimental approaches, we explain the basis for the iron requirement. We further demonstrate the genetic closeness of M. haemophilum and Mycobacterium leprae, the causative agent of leprosy which cannot be cultured in vitro, and we demonstrate methods to genetically manipulate M. haemophilum. These findings pave the way for the use of M. haemophilum as a model to elucidate functions of genes shared with M. leprae

Reactor physics project final report

"September 30, 1970."Statement of responsibility on title-page reads: Editors, M. J. Driscoll, I. Kaplan, D. D. Lanning, N. C. Rasmussen. Contributors: V. K. Agarwala, F. M. Clikeman, M. J. Driscoll, Y. Hukai, L. L. Izzo, I. Kaplan, M. S. Kazimi, D.D. Lanning, T.C. Leung, E.L. McFarland, N.C. Rasmussen, S.S. Seth, G.E. Sullivan, and A.T. SuppleIncludes bibliographical referencesFinal report; January 1, 1968 to September 30, 1970This is the final report in an experimental and theoretical program to develop and apply single- and few-element methods for the determination of reactor lattice parameters. The period covered by the report is January 1, 1968 through September 30, 1970. In addition to summarizing results for the entire contract period, this report also serves as the final annual report; thus, work completed in the period of October 1, 1969 through September 30, 1970 is dealt with in more detail than the earlier work. Methods were developed to measure the heterogeneous parameters 17, [Gamma] [eta] and [Alpha] for single fuel elements immersed in moderator in an exponential tank using foil activation measurements external to the fuel. These methods were applied to clustered fuel rods in D 20 moderator and single fuel rods in H 20 moderator, and the results were extended to and compared with data on complete multi-element lattices reported by other laboratories. Advanced gamma spectrometric methods using Ge(Li) detectors were applied to the analysis of both prompt and fission product decay gammas for the nondestructive analysis of the fuel used in this work. The latter includes both simulated burned fuel containing plutonium and actual burned fuel irradiated to 20,000 MWD/T in the Dresden BWR.U.S. Atomic Energy Commission contract AT (30-1)-394

Reactor physics project progress report

Statement of responsibility on title page reads: Editors: M.J. Driscoll and T.J. Thompson; Contributors: F.M. Clikeman, J.N. Donohew, M.J. Driscoll, J.D. Eckard, T.L. Harper, Y. Hukai, I. Kaplan, C.H. Kim, Y.-M. Lefevre, T.C. Leung, N.R. Ortiz, N.C. Rasmussen, C.S. Rim, S.S. Seth, A.T. Supple C. Takahata, and T.J. Thompson"MIT-3944-1."Progress report; September 30, 1968U.S. Atomic Energy Commission contract AT(30-1)-394

Space and Time in Macroeconomic Panel Data: Young Workers and State-Level Unemployment Revisited

A provocative paper by Shimer (2001) finds that state-level youth shares and unemployment rates are negatively correlated, in contrast to conventional assumptions about demographic effects on labor markets. This paper updates Shimer's regressions and shows that this surprising correlation essentially disappears when the end of the sample period is extended from 1996 to 2005. This shift does not occur because of a change in the underlying economy during the past decade. Rather, the presence of a cross-sectional (that is, spatial) correlation in the state-level data sharply reduces the precision of the earlier estimates, so that the true standard errors are several times larger than those originally reported. Using a longer sample period and some controls for spatial correlation in the regression, point estimates for the youth-share effect on unemployment are positive and close to what a conventional model would imply. Unfortunately, the standard errors remain very large. The difficulty of obtaining precise estimates with these data illustrates a potential pitfall in the use of regional panel data for macroeconomic analysis

A closely-related clade of globally distributed bloom-forming cyanobacteria within the Nostocales

In order to better understand the relationships among current Nostocales cyanobacterial blooms, eight genomes were sequenced from cultured isolates or from environmental metagenomes of recent planktonic Nostocales blooms. Phylogenomic analysis of publicly available sequences placed the new genomes among a group of 15 genomes from four continents in a distinct ADA Glade (Anabaena/Dolichospenruun/Aphanizomenon) within the Nostocales. This Glade contains four species-level groups, two of which include members with both Anabaena-like and Aphanizomenon-flos-aquae-like morphology. The genomes contain many repetitive genetic elements and a sizable pangenome, in which ABC-type transporters are highly represented. Alongside common core genes for photosynthesis, the differentiation of N-2-fixing heterocysts, and the uptake and incorporation of the major nutrients P, N and S, we identified several gene pathways in the pangenome that may contribute to niche partitioning. Genes for problematic secondary metabolites-cyanotoxins and taste-and-odor compounds-were sporadically present, as were other polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) gene clusters. By contrast, genes predicted to encode the ribosomally generated bacteriocin peptides were found in all genomes

Ad-CD40L mobilizes CD4 T cells for the treatment of brainstem tumors

Diffuse Midline Glioma, formerly Diffuse Intrinsic Pontine Glioma (DIPG), is the deadliest pediatric brainstem tumor with median survival of less than one year. Here, we investigated 1) whether direct delivery of adenovirus expressing CD40L (Ad-CD40L) to brainstem tumors would induce immune-mediated tumor clearance and, 2) if so, whether therapy would be associated with a manageable toxicity due to immune-mediated inflammation in the brainstem. Methods Syngeneic gliomas in the brainstems of immune competent mice were treated with Ad-CD40L and survival, toxicity and immune profiles determined. A clinically translatable vector, whose replication would be tightly restricted to tumor cells, rAd-Δ24-CD40L, was tested in human patient-derived Diffuse Midline Gliomas and immunocompetent models. Results Expression of Ad-CD40L restricted to brainstem gliomas by pre-infection induced complete rejection, associated with immune cell infiltration, of which CD4+ T cells were critical for therapy. Direct intra-tumoral injection of Ad-CD40L into established brainstem tumors improved survival and induced some complete cures but with some acute toxicity. RNA-seq analysis showed that Ad-CD40L therapy induced neuroinflammatory immune responses associated with IL-6, IL-1β and TNF-α. Therefore, to generate a vector whose replication, and transgene expression, would be tightly restricted to tumor cells, we constructed rAd-Δ24-CD40L, the backbone of which has already entered clinical trials for Diffuse Midline Glioma. Direct intra-tumoral injection of rAd-Δ24-CD40L, with systemic blockade of IL-6 and IL-1β, generated significant numbers of cures with readily manageable toxicity. Conclusions Virus-mediated delivery of CD40L has the potential to be effective in treating Diffuse Midline Gliomas without obligatory neuroinflammation-associated toxicity