Isolation, characterisation and experimental evolution of phage that infect the horse chestnut tree pathogen, Pseudomonas syringae pv. aesculi

Bleeding canker of horse chestnut trees is a bacterial disease, caused by the bacterium Pseudomonas syringae pv. aesculi, estimated to be present in ~ 50% of UK horse chestnut trees. Currently, the disease has no cure and tree removal can be a common method of reducing inoculum and preventing spread. One potential method of control could be achieved using naturally occurring bacteriophages infective to the causative bacterium. Bacteriophages were isolated from symptomatic and asymptomatic horse chestnut trees in three locations in the South East of England. The phages were found to be belonging to both the Myoviridae and Podoviridae families by RAPD PCR and transmission electron microscopy. Experimental coevolution was carried out to understand the dynamics of bacterial resistance and phage infection and to determine whether new infective phage genotypes would emerge. The phages exhibited different coevolution patterns with their bacterial hosts across time. This approach could be used to generate novel phages for use in biocontrol cocktails in an effort to reduce the potential emergence of bacterial resistance

Landscape-Scale Patterns of Fire and Drought on the High Plains, USA

We examine 31 years (1982-2012) of temperature, precipitation and natural wildfire occurrence data for Federal and Tribal lands to determine landscape-scale patterns of drought and fire on the southern and central High Plains of the western United States. The High Plains states of Colorado, Kansas, Nebraska, New Mexico, Oklahoma, South Dakota, Texas and Wyoming have been in the midst of ongoing extreme drought, experiencing below normal precipitation and above normal temperatures for the past several years. Climate change is predicted to have multiple effects on fire regimes. Longer periods of drought conditions, coupled with hot, dry and windy weather, provide the conditions for wildfire (Ford et al., 2012), and megafires, or large-scale fires that significantly exceed those of recent decades are now occurring in grassland, shrubland and desert ecosystems (Chambers and Pellant, 2008). Our objective is to relate the frequency and size of wildfires to precipitation, temperature and latitudinal gradients to increase understanding of wildfire and drought interactions on the Great Plains in a changing climate

Resolution of the Distance Ambiguity for Galactic HII Regions

We resolve the kinematic distance ambiguity for 266 inner Galaxy HII regions out of a sample of 291 using existing HI and 13CO sky surveys. Our sample contains all HII regions with measured radio recombination line (RRL) emission over the extent of the 13CO Boston University-Five College Radio Astronomy Observatory Galactic Ring Survey (18 deg, < l < 55 deg. and |b| < 1) and contains ultra compact, compact, and diffuse HII regions. We use two methods for resolving the distance ambiguity for each HII region: HI emission/absorption (HIEA) and HI self-absorption (HISA). We find that the HIEA and HISA methods can resolve the distance ambiguity for 72% and 87% of our sample, respectively. When projected onto the Galactic plane, this large sample appears to reveal aspects of Galactic structure, with spiral arm-like features at Galactocentric radii of 4.5 and 6 kpc, and a lack of HII regions within 3.5 kpc of the Galactic center. Our HII regions are approximately in the ratio of 2 to 1 for far verses near distances. The ratio of far to near distances for ultra-compact HII regions is 2.2 to 1. Compact HII regions are preferentially at the near distance; their ratio of far to near distances is 1.6 to 1. Diffuse HII regions are preferentially at the far distance; their ratio of far to near distances is 3.8 to 1. This implies that the distinction between ultra compact and compact HII regions is due largely to distance, and that the large angular size of diffuse HII regions is not due solely to proximity to the Sun.Comment: Accepted to Ap

MicroRNA in prostate cancer: functional importance and potential as circulating biomarkers

BackgroundThis non-systematic review article aims to summarise the progress made in understanding the functional consequences of microRNA (miRNA) dysregulation in prostate cancer development, and the identification of potential miRNA targets as serum biomarkers for diagnosis or disease stratification.ResultsA number of miRNAs have been shown to influence key cellular processes involved in prostate tumourigenesis, including apoptosis-avoidance, cell proliferation and migration and the androgen signalling pathway. An overlapping group of miRNAs have shown differential expression in the serum of patients with prostate cancer of varying stages compared with unaffected individuals. The majority of studies thus far however, involve small numbers of patients and have shown variable and occasionally conflicting resultsConclusionMiRNAs show promise as potential circulating biomarkers in prostate cancer, but larger prospective studies are required to validate particular targets and better define their clinical utility

Esters in ADC linkers: Optimization of stability and lysosomal cleavage

Antibody-drug conjugates (ADCs) present a unique opportunity to increase the safety of highly toxic drugs by utilizing the specificity of antibodies to deliver (typically amine-containing) payloads to specific tissues. However, there are few technologies for attaching alcohol-containing payloads to an antibody. Theoretically, this would be simplest with the use of an ester linkage. However, little is known about the lysosomal and plasma stability of ester linkages on ADCs. Herein, we describe various experiments evaluating this stability in both human/mouse plasma and in lysosomes, as well as the design of a lysosomally cleavable peptide-linked ester. The stability of ester-linked payloads was demonstrated by observing an ester-linked ADC in the presence of lysosomes. The ester remained intact while the antibody backbone was proteolytically degraded. The lysosomal stability of this linkage was additionally confirmed in a cell-based system using SKBR3 cells. We next undertook the design of a novel linker that is stable in mouse plasma, but upon lysosomal uptake, undergoes immolation, resulting in spontaneous ester cleavage. With this research, we hope to further our knowledge of ester linkages in ADCs as well as to develop a feasible way to release an unmodified alcohol-containing drug into a chosen cell type.https://orb.binghamton.edu/research_days_posters_spring2020/1093/thumbnail.jp

The RMS Survey: 13CO observations of candidate massive YSOs in the southern hemisphere

Abridged: The Red MSX Source (RMS) survey is an ongoing multi-wavelength observational programme designed to return a large, well-selected sample of massive young stellar objects (MYSOs). Here we present 13CO observations made towards 854 MYSOs candidates located in the 3rd and 4th quadrants. We detected 13CO emission towards a total of 751 of the 854 RMS sources observed (~88%). In total 2185 emission components are detected above 3$\sigma$ level. Multiple emission profiles are observed towards the majority of these sources - 455 sources (~60%) - with an average of ~4 molecular clouds along the line of sight. These multiple emission features make it difficult to assign a kinematic velocity to many of our sample. We have used archival CS (J=2-1) and maser velocities to resolved the component multiplicity towards 82 sources and have derived a criterion which is used to identify the most likely component for a further 202 multiple component sources. Combined with the single component detections we have obtained unambiguous kinematic velocities towards 580 sources (~80% of the detections). The 171 sources for which we have not been able to determine the kinematic velocity will require additional line data. Using the rotation curve of Brand and Blitz (1993) and their radial velocities we calculate kinematic distances for all components detected.Comment: Summitted to A&A, the resolution of figure 1 has been reduced, samples of Table 3 and Figure 11 are now included but the full version will only be available in the online version of the journa

Therapeutic enhancement of radiation and immunomodulation by gold nanoparticles in triple negative breast cancer

Gold nanoparticles (AuNPs) have been shown to enhance cancer radiotherapy (RT) gain by localizing the absorption of radiation energy in the tumor while sparing surrounding normal tissue from radiation toxicity. Previously, we showed that AuNPs enhanced RT induced DNA damage and cytotoxicity in MCF7 breast cancer cells. Interestingly, we found that cancer cells exhibited a size-dependent AuNPs intracellular localization (4 nm preferentially in the cytoplasm and 14 nm in the nucleus). We extended those studies to an in vivo model and examined the AuNPs effects on RT cytotoxicity, survival and immunomodulation of tumor microenvironment (TME) in human triple negative breast cancer (TNBC) xenograft mouse model. We also explored the significance of nanoparticle size in these AuNPs\u27 effects. Mice treated with RT and RT plus 4 nm or 14 nm AuNPs showed a significant tumor growth delay, compared to untreated animals, while dual RT plus AuNPs treatment exhibited additive effect compared to either RT or AuNPs treatment alone. Survival log-rank test showed significant RT enhancement with 14 nm AuNP alone; however, 4 nm AuNPs did not exhibit RT enhancement. Both sizes of AuNPs enhanced RT induced immunogenic cell death (ICD) that was coupled with significant macrophage infiltration in mice pretreated with 14 nm AuNPs. These results showing significant AuNP size-dependent RT enhancement, as evident by both tumor growth delay and overall survival, reveal additional underlying immunological mechanisms and provide a platform for studying RT multimodal approaches for TNBC that may be combined with immunotherapies, enhancing their effect

Mimicking the electron transfer chain in photosystem II with a molecular triad thermodynamically capable of water oxidation

In the photosynthetic photosystem II, electrons are transferred from the manganese-containing oxygen evolving complex (OEC) to the oxidized primary electron-donor chlorophyll P680•+ by a proton-coupled electron transfer process involving a tyrosine-histidine pair. Proton transfer from the tyrosine phenolic group to a histidine nitrogen positions the redox potential of the tyrosine between those of P680•+ and the OEC. We report the synthesis and time-resolved spectroscopic study of a molecular triad that models this electron transfer. The triad consists of a high-potential porphyrin bearing two pentafluorophenyl groups (PF10), a tetracyanoporphyrin electron acceptor (TCNP), and a benzimidazole-phenol secondary electron-donor (Bi-PhOH). Excitation of PF10 in benzonitrile is followed by singlet energy transfer to TCNP (τ = 41 ps), whose excited state decays by photoinduced electron transfer (τ = 830 ps) to yield Bi-PhOH-PF 10•+-TCNP•-. A second electron transfer reaction follows (τ < 12 ps), giving a final state postulated as BiH+-PhO•-PF10-TCNP•-, in which the phenolic proton now resides on benzimidazole. This final state decays with a time constant of 3.8 μs. The triad thus functionally mimics the electron transfers involving the tyrosine-histidine pair in PSII. The final charge-separated state is thermodynamically capable of water oxidation, and its long lifetime suggests the possibility of coupling systems such as this system to water oxidation catalysts for use in artificial photosynthetic fuel production.Fil: Megiatto, Jackson D.. Arizona State University; Estados UnidosFil: Antoniuk Pablant, Antaeres. Arizona State University; Estados UnidosFil: Sherman, Benjamin D.. Arizona State University; Estados UnidosFil: Kodis, Gerdenis. Arizona State University; Estados UnidosFil: Gervaldo, Miguel Andres. Universidad Nacional de Río Cuarto; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Moore, Thomas A.. Arizona State University; Estados UnidosFil: Moore, Ana L.. Arizona State University; Estados UnidosFil: Gust, Devens. Arizona State University; Estados Unido

The RMS Survey: Distribution and properties of a sample of massive young stars

The Red MSX Source (RMS) survey has identified a large sample of massive young stellar objects (MYSOs) and ultra compact (UC) HII regions from a sample of ~2000 MSX and 2MASS colour selected sources. Using a recent catalogue of molecular clouds derived from the Boston University-Five College Radio Astronomy Observatory Galactic Ring Survey (GRS), and by applying a Galactic scaleheight cut off of 120 pc, we solve the distance ambiguity for RMS sources located within 18\degr 54\degr. These two steps yield kinematic distances to 291 sources out of a possible 326 located within the GRS longitude range. Combining distances and integrated fluxes derived from spectral energy distributions, we estimate luminosities to these sources and find that > 90% are indicative of the presence of a massive star. We find the completeness limit of our sample is ~10^4 Lsun, which corresponds to a zero age main sequence (ZAMS) star with a mass of ~12 Msun. Selecting only these sources, we construct a complete sample of 196 sources. Comparing the properties of the sample of young massive stars with the general population, we find the RMS-clouds are generally larger, more massive, and more turbulent. We examine the distribution of this sub-sample with respect to the location of the spiral arms and the Galactic bar and find them to be spatially correlated. We identify three significant peaks in the source surface density at Galactocentric radii of approximately 4, 6 and 8 kpc, which correspond to the proposed positions of the Scutum, Sagittarius and Perseus spiral arms, respectively. Fitting a scale height to the data we obtain an average value of ~29+-0.5 pc, which agrees well with other reported values in the literature, however, we note a dependence of the scale height on galactocentric radius with it increases from 30 pc to 45 pc between 2.5 and 8.5 kpc.Comment: Accepted for publication by MNRAS. Paper consists of 15 pages including 12 figures and four tables. Full versions of Tables 2 and 3 will only be available online. The resolution of Figure 9 has been reduced - a full resolution version of the paper can be download from here: http://www.ast.leeds.ac.uk/cgi-bin/RMS/RMS_PUBLICATIONS.cg

The ACS Nearby Galaxy Survey Treasury IX. Constraining asymptotic giant branch evolution with old metal-poor galaxies

In an attempt to constrain evolutionary models of the asymptotic giant branch (AGB) phase at the limit of low masses and low metallicities, we have examined the luminosity functions and number ratio between AGB and red giant branch (RGB) stars from a sample of resolved galaxies from the ACS Nearby Galaxy Survey Treasury (ANGST). This database provides HST optical photometry together with maps of completeness, photometric errors, and star formation histories for dozens of galaxies within 4 Mpc. We select 12 galaxies characterized by predominantly metal-poor populations as indicated by a very steep and blue RGB, and which do not present any indication of recent star formation in their color--magnitude diagrams. Thousands of AGB stars brighter than the tip of the RGB (TRGB) are present in the sample (between 60 and 400 per galaxy), hence the Poisson noise has little impact in our measurements of the AGB/RGB ratio. We model the photometric data with a few sets of thermally pulsing AGB (TP-AGB) evolutionary models with different prescriptions for the mass loss. This technique allows us to set stringent constraints to the TP-AGB models of low-mass metal-poor stars (with M<1.5 Msun, [Fe/H]<~-1.0). Indeed, those which satisfactorily reproduce the observed AGB/RGB ratios have TP-AGB lifetimes between 1.2 and 1.8 Myr, and finish their nuclear burning lives with masses between 0.51 and 0.55 Msun. This is also in good agreement with recent observations of white dwarf masses in the M4 old globular cluster. These constraints can be added to those already derived from Magellanic Cloud star clusters as important mileposts in the arduous process of calibrating AGB evolutionary models.Comment: To appear in ApJ, a version with better resolution is in http://stev.oapd.inaf.it/~lgirardi/rgbagb.pd