Structural Characterization of HIP2 Enzyme Interactions in Ubiquitination

The ubiquitin proteolysis pathway utilizes three enzymes, an E1 activating enzyme, an E2 conjugating enzyme and an E3 ligating enzyme, to respectively activate, transfer and ligate ubiquitin (Ub) onto a substrate protein. The creation of a K48-linked poly-Ub chain on a substrate will target this protein to be degraded by the 26S proteosome. E2 conjugating enzymes are central proteins in this pathway and interact with the E1 and E3 enzymes to perform Ub transfer. The mechanism by which Ub molecules are interconnected remains poorly understood. The E2 enzymes HIP2 and Ubc1 have been shown to create poly-Ub chains in the absence of E3 enzymes and substrates. In this thesis, HIP2 and Ubc1 were investigated through physical and structural methods to clarify their mechanism of poly-Ub chain assembly. The study of HIP2 and Ubc1 was aided by the formation and purification of stable HIP2-Ub and Ubc1-Ub disulphide linked complexes that closely resemble the HIP2~Ub and Ubc1~Ub thiolester intermediates. The physical techniques of sedimentation equilibrium and SAXS determined that HIP2 and Ubc1 as well as their disulphide complexes are predominantly monomeric. Activity assays were also performed on these enzymes indicating that the E2~Ub thiolester is the sole species required to create poly-Ub chains. Additionally, these assays determined that both free Ub and E2-Ub complexes could act as Ub acceptors for poly-ubiquitin chain extension. NMR experiments were also performed through the use of isotopically labelled HIP2, HIP2-Ub and HIP2-Ub2 complexes. NMR chemical shift perturbation experiments identified significant intramolecular interactions between HIP2 and Ub in both HIP2-Ub and HIP2-Ub2 complexes. The intramolecular interaction within HIP2-Ub2 utilizes a C-terminal Ub-associated (UBA) domain and this domain is not present in other human E2 enzymes. These intramolecular interactions indicate the HIP2-Ub and HIP2-Ub2 complexes behave predominantly as Ub donors within poly-Ub chain formation. These results have allowed the formulation of mechanisms to describe HIP2 and Ubc1 function. The determination of these mechanisms is especially important for HIP2, as its function has been associated with the progression of both Huntington’s and Alzheimer’s disease

Binary black hole initial data from matched asymptotic expansions

We present an approximate metric for a binary black hole spacetime to construct initial data for numerical relativity. This metric is obtained by asymptotically matching a post-Newtonian metric for a binary system to a perturbed Schwarzschild metric for each hole. In the inner zone near each hole, the metric is given by the Schwarzschild solution plus a quadrupolar perturbation corresponding to an external tidal gravitational field. In the near zone, well outside each black hole but less than a reduced wavelength from the center of mass of the binary, the metric is given by a post-Newtonian expansion including the lowest-order deviations from flat spacetime. When the near zone overlaps each inner zone in a buffer zone, the post-Newtonian and perturbed Schwarzschild metrics can be asymptotically matched to each other. By demanding matching (over a 4-volume in the buffer zone) rather than patching (choosing a particular 2-surface in the buffer zone), we guarantee that the errors are small in all zones. The resulting piecewise metric is made formally $C^\infty$ with smooth transition functions so as to obtain the finite extrinsic curvature of a 3-slice. In addition to the metric and extrinsic curvature, we present explicit results for the lapse and the shift, which can be used as initial data for numerical simulations. This initial data is not accurate all the way to the asymptotically flat ends inside each hole, and therefore must be used with evolution codes which employ black hole excision rather than puncture methods. This paper lays the foundations of a method that can be sraightforwardly iterated to obtain initial data to higher perturbative order.Comment: 24 pages, 15 figures. Replaced with published version. Major editing of text, no major change to the physic

Empirical ugri-UBVRc Transformations for Galaxies

We present empirical color transformations between Sloan Digital Sky Survey ugri and Johnson-Cousins UBVRc photometry for nearby galaxies (D < 11 Mpc). We use the Local Volume Legacy (LVL) galaxy sample where there are 90 galaxies with overlapping observational coverage for these two filter sets. The LVL galaxy sample consists of normal, non-starbursting galaxies. We also examine how well the LVL galaxy colors are described by previous transformations derived from standard calibration stars and model-based galaxy templates. We find significant galaxy color scatter around most of the previous transformation relationships. In addition, the previous transformations show systematic offsets between transformed and observed galaxy colors which are visible in observed color-color trends. The LVL-based $galaxy$ transformations show no systematic color offsets and reproduce the observed color-color galaxy trends.Comment: Accepted for publication in MNRAS (9 pages, 6 figures, 4 tables

Spitzer Local Volume Legacy (LVL) SEDs and Physical Properties

We present the panchromatic spectral energy distributions (SEDs) of the Local Volume Legacy (LVL) survey which consists of 258 nearby galaxies ($D<$11 Mpc). The wavelength coverage spans the ultraviolet to the infrared (1500 $\textrm{\AA}$ to 24 $\mu$m) which is utilized to derive global physical properties (i.e., star formation rate, stellar mass, internal extinction due to dust.). With these data, we find color-color relationships and correlated trends between observed and physical properties (i.e., optical magnitudes and dust properties, optical color and specific star formation rate, and ultraviolet-infrared color and metallicity). The SEDs are binned by different galaxy properties to reveal how each property affects the observed shape of these SEDs. In addition, due to the volume-limited nature of LVL, we utilize the dwarf-dominated galaxy sample to test star formation relationships established with higher-mass galaxy samples. We find good agreement with the star-forming "main-sequence" relationship, but find a systematic deviation in the infrared "main-sequence" at low luminosities. This deviation is attributed to suppressed polycyclic aromatic hydrocarbon (PAH) formation in low metallicity environments and/or the destruction of PAHs in more intense radiation fields occurring near a suggested threshold in sSFR at a value of log($sSFR$) $\sim$ $-$10.2.Comment: Accepted for publication in MNRAS (15 pages, 14 figures, 1 table

The Spitzer Local Volume Legacy (LVL) Global Optical Photometry

We present the global optical photometry of 246 galaxies in the Local Volume Legacy (LVL) survey. The full volume-limited sample consists of 258 nearby (D < 11 Mpc) galaxies whose absolute B-band magnitude span a range of -9.6 < M_B < -20.7 mag. A composite optical (UBVR) data set is constructed from observed UBVR and SDSS ugriz imaging, where the ugriz magnitudes are transformed into UBVR. We present photometry within three galaxy apertures defined at UV, optical, and IR wavelengths. Flux comparisons between these apertures reveal that the traditional optical R25 galaxy apertures do not fully encompass extended sources. Using the larger IR apertures we find color-color relationships where later-type spiral and irregular galaxies tend to be bluer than earlier-type galaxies. These data provide the missing optical emission from which future LVL studies can construct the full panchromatic (UV-optical-IR) spectral energy distributions.Comment: Accepted for publication in MNRAS (9 pages, 5 figures, 5 tables

North American megadroughts in the Common Era: reconstructions and simulations

During the Medieval Climate Anomaly (MCA), Western North America experienced episodes of intense aridity that persisted for multiple decades or longer. These megadroughts are well documented in many proxy records, but the causal mechanisms are poorly understood. General circulation models (GCMs) simulate megadroughts, but do not reproduce the temporal clustering of events during the MCA, suggesting they are not caused by the time history of volcanic or solar forcing. Instead, GCMs generate megadroughts through (1) internal atmospheric variability, (2) sea-surface temperatures, and (3) land surface and dust aerosol feedbacks. While no hypothesis has been definitively rejected, and no GCM has accurately reproduced all features (e.g., timing, duration, and extent) of any specific megadrought, their persistence suggests a role for processes that impart memory to the climate system (land surface and ocean dynamics). Over the 21st century, GCMs project an increase in the risk of megadrought occurrence through greenhouse gas forced reductions in precipitation and increases in evaporative demand. This drying is robust across models and multiple drought indicators, but major uncertainties still need to be resolved. These include the potential moderation of vegetation evaporative losses at higher atmospheric [CO₂], variations in land surface model complexity, and decadal to multidecadal modes of natural climate variability that could delay or advance onset of aridification over the the next several decades. Because future droughts will arise from both natural variability and greenhouse gas forced trends in hydroclimate, improving our understanding of the natural drivers of persistent multidecadal megadroughts should be a major research priority

The discomforting rise of ' public geographies': a 'public' conversation.

In this innovative and provocative intervention, the authors explore the burgeoning ‘public turn’ visible across the social sciences to espouse the need to radically challenge and reshape dominant and orthodox visions of ‘the academy’, academic life, and the role and purpose of the academic

Flowering Date of Taxonomic Families Predicts Phenological Sensitivity to Temperature: Implications for Forecasting the Effects of Climate Change on Unstudied Taxa

Premise of the study: Numerous long-term studies in seasonal habitats have tracked interannual variation in fi rst fl owering date (FFD) in relation to climate, documenting the effect of warming on the FFD of many species. Despite these efforts, long-term phenological observations are still lacking for many species. If we could forecast responses based on taxonomic affi nity, however, then we could leverage existing data to predict the climate-related phenological shifts of many taxa not yet studied; Methods: We examined phenological time series of 1226 species occurrences (1031 unique species in 119 families) across seven sites in North America and England to determine whether family membership (or family mean FFD) predicts the sensitivity of FFD to standardized interannual changes in temperature and precipitation during seasonal periods before fl owering and whether families differ signifi cantly in the direction of their phenological shifts; Key results: Patterns observed among species within and across sites are mirrored among family means across sites; earlyfl owering families advance their FFD in response to warming more than late-fl owering families. By contrast, we found no consistent relationships among taxa between mean FFD and sensitivity to precipitation as measured here; Conclusions: Family membership can be used to identify taxa of high and low sensitivity to temperature within the seasonal, temperate zone plant communities analyzed here. The high sensitivity of early-fl owering families (and the absence of earlyfl owering families not sensitive to temperature) may refl ect plasticity in fl owering time, which may be adaptive in environments where early-season conditions are highly variable among years

Placing the east-west North American aridity gradient in a multi-century context

Instrumental records indicate a century-long trend towards drying over western North America and wetting over eastern North America. A continuation of these trends into the future would have significant hydroclimatic and socioeconomic consequences in both the semi-arid Southwest and humid East. Using tree-ring reconstructions and hydrologic simulations of summer soil moisture, we evaluate and contextualize the modern summer aridity gradient within its natural range of variability established over the past 600 years and evaluate the effects of observed and anthropogenic precipitation, temperature, and humidity trends. The 2001–2020 positive (wet east-dry west) aridity gradient was larger than any 20 year period since 1400 CE, preceded by the most negative (wet west-dry east) aridity gradient during 1976–1995, leading to a strong multi-decade reversal in aridity gradient anomalies that was rivaled only by a similar event in the late-16th century. The 2001–2020 aridity gradient was dominated by long-term summer precipitation increases in the Midwest and Northeast, with smaller contributions from more warming in the West than the East and spring precipitation decreases in the Southwest. Multi-model mean climate simulations from Coupled Model Intercomparison Project 6 experiments suggest anthropogenic climate trends should not have strongly affected the aridity gradient thus far. However, there is high uncertainty due to inter-model disagreement on anthropogenic precipitation trends. The recent strengthening of the observed aridity gradient, its increasing dependence on precipitation variability, and disagreement in modeled anthropogenic precipitation trends reveal significant uncertainties in how water resource availability will change across North America in the coming decades